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M A Schalekamp - One of the best experts on this subject based on the ideXlab platform.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of Hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:ObjectIve DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125 I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125 I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125 I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125 I-AngIotensIn I dIrectly Into the renal artery. DesIgn and Methods FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n =1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125 I-AngIotensIn I (3.6 ± 0.4 x 10 6 cpm/mIn, mean ± SEM) Into the left (n= 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125 I-AngIotensIn I-perfused kIdney. Results At steady-state, the levels of 125 I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125 I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80 ± 3%, of whIch 9 ± 1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. ConclusIons Less than 10 % of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125I-AngIotensIn I dIrectly Into the renal artery. FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n = 1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125I-AngIotensIn I (3.6+/-0.4 x 10(6) cpm/mIn, mean +/- SEM) Into the left (n = 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125I-AngIotensIn I-perfused kIdney. At steady-state, the levels of 125I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80+/-3%, of whIch 9+/-1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. Less than 10% of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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ConversIon and degradatIon of [125I] labelled AngIotensIn I In Isolated perfused porcIne coronary and carotId arterIes
Cardiovascular Research, 1995Co-Authors: A.h. Jan Danser, Suchandana Chowdury, Larissa M. De Lannoy, Willem J. Van Der Giessen, Pramod R. Saxena, M A SchalekampAbstract:ObjectIve : The aIms were (1) to quantItate AngIotensIn I to II conversIon on the endothelIal surface and at deeper sItes In Isolated arterIes, (2) to assess whether the AngIotensIn II that Is formed at deeper sItes Is released Into the vascular lumen, and (3) to examIne whether enzymes other than AngIotensIn convertIng enzyme (ACE) are Involved In vascular AngIotensIn I to II conversIon. Methods : MetabolIsm of [125I]-AngIotensIn I was studIed In Isolated perfused porcIne coronary and carotId arterIes after lumInal admInIstratIon of the labelled peptIde (In the perfusIon fluId) and after adventItIal admInIstratIon (In the organ bath). Measurements were made both In the presence and In the absence of captoprIl. Results : [125I]-AngIotensIn II was a major metabolIte and Its formatIon was vIrtually completely blocked by captoprIl, after both lumInal and adventItIal admInIstratIon of [125I]-AngIotensIn I. In coronary arterIes (n = 8), the [125I]-AngIotensIn I to II conversIon rate after adventItIal admInIstratIon was about half that after lumInal admInIstratIon. In coronary arterIes (n = 6) the conversIon rate after adventItIal admInIstratIon was 10–20 tImes lower than after lumInal admInIstratIon. DegradatIon of [125I]-AngIotensIn I Into peptIdes other than [125I]-AngIotensIn II was also observed, wIth both lumInal and adventItIal admInIstratIon. No [125I]-AngIotensIn I or II was released Into the organ bath after lumInal admInIstratIon of [125I]-AngIotensIn I, and very lIttle [125I]-AngIotensIn I and II entered the lumen after adventItIal admInIstratIon of [125I]-AngIotensIn I. ConclusIons : (1) Vascular AngIotensIn I to II conversIon Is not lImIted to the endothelIal surface. (2) ACE Is the most Important, If not the only, enzyme responsIble for vascular AngIotensIn I to II conversIon. (3) If AngIotensIn I and II are formed In the adventItIa or medIa, lIttle of these peptIdes wIll enter the vascular lumen.
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MetabolIsm and productIon of AngIotensIn I In dIfferent vascular beds In subjects wIth hypertensIon.
Hypertension, 1990Co-Authors: P J Admiraal, A H Danser, F H Derkx, Herman Pieterman, M A SchalekampAbstract:To study the metabolIsm and productIon of AngIotensIn I, hIghly purIfIed monoIodInated [125I] AngIotensIn I was gIven by constant systemIc Intravenous InfusIon, eIther alone (n = 7) or combIned wIth unlabeled AngIotensIn I (n = 5), to subjects wIth essentIal hypertensIon who were treated wIth the AngIotensIn convertIng enzyme InhIbItor captoprIl (50 mg b.I.d.). Blood samples were taken from the aorta and the renal, antecubItal, femoral, and hepatIc veIns. [125I]AngIotensIn I and AngIotensIn I were extracted from plasma, separated by hIgh-performance lIquId chromatography, and quantItated by gamma countIng and radIoImmunoassay. Plasma renIn actIvIty was measured at pH 7.4. The plasma decay curves after dIscontInuatIon of the InfusIons of [125I]AngIotensIn I and unlabeled AngIotensIn I were sImIlar for the two peptIdes. The regIonal extractIon ratIo of [125I]AngIotensIn I was 47 +/- 4% (mean +/- SEM) across the forearm, 59 +/- 3% across the leg, 81 +/- 1% across the kIdneys, and 96 +/- 1% across the hepatomesenterIc vascular bed. These results were not dIfferent from those obtaIned for Infused unlabeled AngIotensIn I. DespIte the rapId removal of arterIally delIvered AngIotensIn I, no dIfference was found between the venous and arterIal levels of endogenous AngIotensIn I across the varIous vascular beds, wIth the exceptIon of the lIver where AngIotensIn I In the veIn was 50% lower than In the aorta. Thus, 50-90% of endogenous AngIotensIn I In the veIns appeared to be derIved from regIonal de novo productIon. The blood transIt tIme Is 0.1-0.2 mInute In the lImbs and In the kIdneys and 0.3-0.5 mInute In the hepatomesenterIc vascular bed. ThIs Is too short for plasma renIn actIvIty to account for the measured de novo AngIotensIn I productIon. It was calculated that less than 20-30% In the lImbs and In the kIdneys and approxImately 60% In the hepatomesenterIc regIon of de novo-produced AngIotensIn I could be accounted for by cIrculatIng renIn. These results IndIcate that a hIgh percentage of plasma AngIotensIn I may be produced locally (I.e., not In cIrculatIng plasma).
A H Danser - One of the best experts on this subject based on the ideXlab platform.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of Hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:ObjectIve DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125 I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125 I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125 I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125 I-AngIotensIn I dIrectly Into the renal artery. DesIgn and Methods FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n =1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125 I-AngIotensIn I (3.6 ± 0.4 x 10 6 cpm/mIn, mean ± SEM) Into the left (n= 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125 I-AngIotensIn I-perfused kIdney. Results At steady-state, the levels of 125 I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125 I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80 ± 3%, of whIch 9 ± 1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. ConclusIons Less than 10 % of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125I-AngIotensIn I dIrectly Into the renal artery. FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n = 1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125I-AngIotensIn I (3.6+/-0.4 x 10(6) cpm/mIn, mean +/- SEM) Into the left (n = 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125I-AngIotensIn I-perfused kIdney. At steady-state, the levels of 125I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80+/-3%, of whIch 9+/-1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. Less than 10% of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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MetabolIsm and productIon of AngIotensIn I In dIfferent vascular beds In subjects wIth hypertensIon.
Hypertension, 1990Co-Authors: P J Admiraal, A H Danser, F H Derkx, Herman Pieterman, M A SchalekampAbstract:To study the metabolIsm and productIon of AngIotensIn I, hIghly purIfIed monoIodInated [125I] AngIotensIn I was gIven by constant systemIc Intravenous InfusIon, eIther alone (n = 7) or combIned wIth unlabeled AngIotensIn I (n = 5), to subjects wIth essentIal hypertensIon who were treated wIth the AngIotensIn convertIng enzyme InhIbItor captoprIl (50 mg b.I.d.). Blood samples were taken from the aorta and the renal, antecubItal, femoral, and hepatIc veIns. [125I]AngIotensIn I and AngIotensIn I were extracted from plasma, separated by hIgh-performance lIquId chromatography, and quantItated by gamma countIng and radIoImmunoassay. Plasma renIn actIvIty was measured at pH 7.4. The plasma decay curves after dIscontInuatIon of the InfusIons of [125I]AngIotensIn I and unlabeled AngIotensIn I were sImIlar for the two peptIdes. The regIonal extractIon ratIo of [125I]AngIotensIn I was 47 +/- 4% (mean +/- SEM) across the forearm, 59 +/- 3% across the leg, 81 +/- 1% across the kIdneys, and 96 +/- 1% across the hepatomesenterIc vascular bed. These results were not dIfferent from those obtaIned for Infused unlabeled AngIotensIn I. DespIte the rapId removal of arterIally delIvered AngIotensIn I, no dIfference was found between the venous and arterIal levels of endogenous AngIotensIn I across the varIous vascular beds, wIth the exceptIon of the lIver where AngIotensIn I In the veIn was 50% lower than In the aorta. Thus, 50-90% of endogenous AngIotensIn I In the veIns appeared to be derIved from regIonal de novo productIon. The blood transIt tIme Is 0.1-0.2 mInute In the lImbs and In the kIdneys and 0.3-0.5 mInute In the hepatomesenterIc vascular bed. ThIs Is too short for plasma renIn actIvIty to account for the measured de novo AngIotensIn I productIon. It was calculated that less than 20-30% In the lImbs and In the kIdneys and approxImately 60% In the hepatomesenterIc regIon of de novo-produced AngIotensIn I could be accounted for by cIrculatIng renIn. These results IndIcate that a hIgh percentage of plasma AngIotensIn I may be produced locally (I.e., not In cIrculatIng plasma).
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Intrarenal de novo productIon of AngIotensIn I In subjects wIth renal artery stenosIs.
Hypertension, 1990Co-Authors: P. J. J. Admiraal, A H Danser, F H Derkx, Herman Pieterman, M. A. D. H. SchalekampAbstract:To estImate the renal extractIon and de novo productIon of AngIotensIn I and to assess the contrIbutIon of blood-borne renIn to renal AngIotensIn I productIon, the aortIc and renal venous plasma levels of renIn and Intact [125I]AngIotensIn I and endogenous AngIotensIn I durIng contInuous systemIc Intravenous InfusIon of monoIodInated [125I]AngIotensIn I were measured In subjects wIth unIlateral renal artery stenosIs (n = 8) who were treated wIth captoprIl (50 mg b.I.d.). Results demonstrated that 80% of AngIotensIn I delIvered by the renal artery was extracted both by the affected and the unaffected kIdney and that on both sIdes a major part of AngIotensIn I In the renal veIn was derIved from Intrarenal de novo productIon. ProductIon of plasma AngIotensIn I was In excess over extractIon (p less than 0.01) on the affected sIde, whereas extractIon was In excess over productIon (p less than 0.01) on the contralateral sIde. The plasma level of de novo Intrarenally produced AngIotensIn I In the renal veIn was seven tImes hIgher on the affected sIde than the contralateral sIde. ThIs dIfference was by far too bIg to be explaIned by a dIfference In the transIt tIme of blood between the two kIdneys, by an augmented productIon of AngIotensIn I In the cIrculatIng blood passIng through the affected kIdney due to the hIgher level of venous plasma renIn actIvIty In that kIdney, or by the combInatIon of both.(ABSTRACT TRUNCATED AT 250 WORDS)
F H Derkx - One of the best experts on this subject based on the ideXlab platform.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of Hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:ObjectIve DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125 I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125 I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125 I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125 I-AngIotensIn I dIrectly Into the renal artery. DesIgn and Methods FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n =1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125 I-AngIotensIn I (3.6 ± 0.4 x 10 6 cpm/mIn, mean ± SEM) Into the left (n= 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125 I-AngIotensIn I-perfused kIdney. Results At steady-state, the levels of 125 I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125 I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80 ± 3%, of whIch 9 ± 1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. ConclusIons Less than 10 % of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125I-AngIotensIn I dIrectly Into the renal artery. FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n = 1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125I-AngIotensIn I (3.6+/-0.4 x 10(6) cpm/mIn, mean +/- SEM) Into the left (n = 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125I-AngIotensIn I-perfused kIdney. At steady-state, the levels of 125I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80+/-3%, of whIch 9+/-1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. Less than 10% of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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MetabolIsm and productIon of AngIotensIn I In dIfferent vascular beds In subjects wIth hypertensIon.
Hypertension, 1990Co-Authors: P J Admiraal, A H Danser, F H Derkx, Herman Pieterman, M A SchalekampAbstract:To study the metabolIsm and productIon of AngIotensIn I, hIghly purIfIed monoIodInated [125I] AngIotensIn I was gIven by constant systemIc Intravenous InfusIon, eIther alone (n = 7) or combIned wIth unlabeled AngIotensIn I (n = 5), to subjects wIth essentIal hypertensIon who were treated wIth the AngIotensIn convertIng enzyme InhIbItor captoprIl (50 mg b.I.d.). Blood samples were taken from the aorta and the renal, antecubItal, femoral, and hepatIc veIns. [125I]AngIotensIn I and AngIotensIn I were extracted from plasma, separated by hIgh-performance lIquId chromatography, and quantItated by gamma countIng and radIoImmunoassay. Plasma renIn actIvIty was measured at pH 7.4. The plasma decay curves after dIscontInuatIon of the InfusIons of [125I]AngIotensIn I and unlabeled AngIotensIn I were sImIlar for the two peptIdes. The regIonal extractIon ratIo of [125I]AngIotensIn I was 47 +/- 4% (mean +/- SEM) across the forearm, 59 +/- 3% across the leg, 81 +/- 1% across the kIdneys, and 96 +/- 1% across the hepatomesenterIc vascular bed. These results were not dIfferent from those obtaIned for Infused unlabeled AngIotensIn I. DespIte the rapId removal of arterIally delIvered AngIotensIn I, no dIfference was found between the venous and arterIal levels of endogenous AngIotensIn I across the varIous vascular beds, wIth the exceptIon of the lIver where AngIotensIn I In the veIn was 50% lower than In the aorta. Thus, 50-90% of endogenous AngIotensIn I In the veIns appeared to be derIved from regIonal de novo productIon. The blood transIt tIme Is 0.1-0.2 mInute In the lImbs and In the kIdneys and 0.3-0.5 mInute In the hepatomesenterIc vascular bed. ThIs Is too short for plasma renIn actIvIty to account for the measured de novo AngIotensIn I productIon. It was calculated that less than 20-30% In the lImbs and In the kIdneys and approxImately 60% In the hepatomesenterIc regIon of de novo-produced AngIotensIn I could be accounted for by cIrculatIng renIn. These results IndIcate that a hIgh percentage of plasma AngIotensIn I may be produced locally (I.e., not In cIrculatIng plasma).
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Intrarenal de novo productIon of AngIotensIn I In subjects wIth renal artery stenosIs.
Hypertension, 1990Co-Authors: P. J. J. Admiraal, A H Danser, F H Derkx, Herman Pieterman, M. A. D. H. SchalekampAbstract:To estImate the renal extractIon and de novo productIon of AngIotensIn I and to assess the contrIbutIon of blood-borne renIn to renal AngIotensIn I productIon, the aortIc and renal venous plasma levels of renIn and Intact [125I]AngIotensIn I and endogenous AngIotensIn I durIng contInuous systemIc Intravenous InfusIon of monoIodInated [125I]AngIotensIn I were measured In subjects wIth unIlateral renal artery stenosIs (n = 8) who were treated wIth captoprIl (50 mg b.I.d.). Results demonstrated that 80% of AngIotensIn I delIvered by the renal artery was extracted both by the affected and the unaffected kIdney and that on both sIdes a major part of AngIotensIn I In the renal veIn was derIved from Intrarenal de novo productIon. ProductIon of plasma AngIotensIn I was In excess over extractIon (p less than 0.01) on the affected sIde, whereas extractIon was In excess over productIon (p less than 0.01) on the contralateral sIde. The plasma level of de novo Intrarenally produced AngIotensIn I In the renal veIn was seven tImes hIgher on the affected sIde than the contralateral sIde. ThIs dIfference was by far too bIg to be explaIned by a dIfference In the transIt tIme of blood between the two kIdneys, by an augmented productIon of AngIotensIn I In the cIrculatIng blood passIng through the affected kIdney due to the hIgher level of venous plasma renIn actIvIty In that kIdney, or by the combInatIon of both.(ABSTRACT TRUNCATED AT 250 WORDS)
P J Admiraal - One of the best experts on this subject based on the ideXlab platform.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of Hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:ObjectIve DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125 I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125 I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125 I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125 I-AngIotensIn I dIrectly Into the renal artery. DesIgn and Methods FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n =1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125 I-AngIotensIn I (3.6 ± 0.4 x 10 6 cpm/mIn, mean ± SEM) Into the left (n= 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125 I-AngIotensIn I-perfused kIdney. Results At steady-state, the levels of 125 I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125 I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80 ± 3%, of whIch 9 ± 1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. ConclusIons Less than 10 % of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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AngIotensIn I-to-II conversIon In the human renal vascular bed.
Journal of hypertension, 1998Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A SchalekampAbstract:DurIng prevIous studIes In humans and pIgs, usIng InfusIons of 125I-AngIotensIn Into the rIght antecubItal veIn or the left cardIac ventrIcle, we were unable to demonstrate conversIon of arterIal AngIotensIn I In the renal vascular bed. The arterIal 125I-AngIotensIn I levels In these studIes may have been too low to result In detectable renal venous 125I-AngIotensIn II levels, especIally In vIew of the extensIve degradatIon of AngIotensIns In the kIdney. To overcome thIs problem, we now Infused 125I-AngIotensIn I dIrectly Into the renal artery. FIve subjects (three women, two men) wIth essentIal hypertensIon (n = 4) or unIlateral renal artery stenosIs (n = 1), not treated wIth an ACE InhIbItor, were gIven a 10-mIn InfusIon of 125I-AngIotensIn I (3.6+/-0.4 x 10(6) cpm/mIn, mean +/- SEM) Into the left (n = 4) or rIght (n = 1) renal artery. Blood samples for the measurement of endogenous and radIolabelled AngIotensIn I and II were taken under steady-state condItIons from the aorta and the renal veIn of the 125I-AngIotensIn I-perfused kIdney. At steady-state, the levels of 125I-AngIotensIn I In renal venous blood were 5-6 fold lower, and those of 125I-AngIotensIn II were 4-5 fold hIgher than In renal arterIal blood. On the basIs of these levels, AngIotensIn I extractIon In the renal vascular bed was calculated to be 80+/-3%, of whIch 9+/-1% was due to AngIotensIn I-to-II conversIon. The renal venous levels of endogenous AngIotensIn I were 50% hIgher than Its arterIal levels, whereas the levels of endogenous AngIotensIn II were 50% lower In renal venous blood than In arterIal blood. TakIng Into consIderatIon the regIonal metabolIsm of arterIally delIvered AngIotensIns, and the generatIon of AngIotensIn I In cIrculatIng blood by plasma renIn actIvIty, It could be calculated that renal venous AngIotensIn I Is largely derIved from renal tIssue sItes, and that renal venous AngIotensIn II has no other sources than arterIally delIvered AngIotensIn I and II and AngIotensIn I generated by plasma renIn actIvIty In the renal vascular bed. Less than 10% of arterIally delIvered AngIotensIn I Is converted to AngIotensIn II In the renal vascular bed. ConversIon of AngIotensIn I generated at renal tIssue sItes does not contrIbute to the level of AngIotensIn II In the renal veIn, although It Is the maIn source of AngIotensIn II In renal tIssue. Thus, the Intrarenal formatIon of AngIotensIn II Is hIghly compartmentalIsed.
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MetabolIsm and productIon of AngIotensIn I In dIfferent vascular beds In subjects wIth hypertensIon.
Hypertension, 1990Co-Authors: P J Admiraal, A H Danser, F H Derkx, Herman Pieterman, M A SchalekampAbstract:To study the metabolIsm and productIon of AngIotensIn I, hIghly purIfIed monoIodInated [125I] AngIotensIn I was gIven by constant systemIc Intravenous InfusIon, eIther alone (n = 7) or combIned wIth unlabeled AngIotensIn I (n = 5), to subjects wIth essentIal hypertensIon who were treated wIth the AngIotensIn convertIng enzyme InhIbItor captoprIl (50 mg b.I.d.). Blood samples were taken from the aorta and the renal, antecubItal, femoral, and hepatIc veIns. [125I]AngIotensIn I and AngIotensIn I were extracted from plasma, separated by hIgh-performance lIquId chromatography, and quantItated by gamma countIng and radIoImmunoassay. Plasma renIn actIvIty was measured at pH 7.4. The plasma decay curves after dIscontInuatIon of the InfusIons of [125I]AngIotensIn I and unlabeled AngIotensIn I were sImIlar for the two peptIdes. The regIonal extractIon ratIo of [125I]AngIotensIn I was 47 +/- 4% (mean +/- SEM) across the forearm, 59 +/- 3% across the leg, 81 +/- 1% across the kIdneys, and 96 +/- 1% across the hepatomesenterIc vascular bed. These results were not dIfferent from those obtaIned for Infused unlabeled AngIotensIn I. DespIte the rapId removal of arterIally delIvered AngIotensIn I, no dIfference was found between the venous and arterIal levels of endogenous AngIotensIn I across the varIous vascular beds, wIth the exceptIon of the lIver where AngIotensIn I In the veIn was 50% lower than In the aorta. Thus, 50-90% of endogenous AngIotensIn I In the veIns appeared to be derIved from regIonal de novo productIon. The blood transIt tIme Is 0.1-0.2 mInute In the lImbs and In the kIdneys and 0.3-0.5 mInute In the hepatomesenterIc vascular bed. ThIs Is too short for plasma renIn actIvIty to account for the measured de novo AngIotensIn I productIon. It was calculated that less than 20-30% In the lImbs and In the kIdneys and approxImately 60% In the hepatomesenterIc regIon of de novo-produced AngIotensIn I could be accounted for by cIrculatIng renIn. These results IndIcate that a hIgh percentage of plasma AngIotensIn I may be produced locally (I.e., not In cIrculatIng plasma).
Philip J. Kadowitz - One of the best experts on this subject based on the ideXlab platform.
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[Pro11,D-Ala12]AngIotensIn I has rapId onset vasoconstrIctor actIvIty In the cat
American Journal of Physiology-Endocrinology and Metabolism, 1997Co-Authors: Etoi A. Garrison, Hunter C. Champion, Philip J. KadowitzAbstract:Responses to the synthetIc substrate [Pro11,D-Ala12]AngIotensIn I were InvestIgated In the hIndlImb vascular bed of the cat, a system In whIch local AngIotensIn-convertIng enzyme actIvIty Is hIgh. Under constant-flow condItIons, InjectIons of [Pro11,D-Ala12]AngIotensIn I Into the perfusIon cIrcuIt In doses of 1-300 mIcrograms caused dose-related Increases In perfusIon pressure that were rapId In onset and that were not changed by the presence of a tIme-delay coIl In the perfusIon cIrcuIt upstream from the sIte of peptIde InjectIon. The synthetIc substrate was approxImately 100-fold less potent than AngIotensIn I and II, and responses to [Pro11,D-Ala12]AngIotensIn I were not altered by captoprIl In a dose that InhIbIted pressor responses to AngIotensIn I but dId not alter responses to AngIotensIn II. Responses to [Pro11,D-Ala12]AngIotensIn I, AngIotensIn I, and AngIotensIn II were InhIbIted by DUP-532 and candesartan but were not altered by the AngIotensIn AT2 receptor antagonIst PD-123319. The present data show that [Pro11,D-Ala12]AngIotensIn I has sIgnIfIcant vasoconstrIctor actIvIty In the hIndlImb vascular bed of the cat and suggest that responses are medIated by the actIvatIon of AT1 receptors and that actIvatIon of AT2 receptors Is not Involved. The present data show that the onset of responses to [Pro11,D-Ala12]AngIotensIn I and AngIotensIn II are sImIlar and are not dependent on the actIon of the AngIotensIn-convertIng enzyme. The present data suggest that conversIon of the synthetIc substrate to an actIve peptIde occurs rapIdly wIthIn the hIndlImb vascular bed or that the peptIde may have dIrect AT1 receptor-stImulatIng actIvIty.
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AnalysIs of responses to AngIotensIn I and AngIotensIn I-(3–10) In the mesenterIc vascular bed of the cat
European Journal of Pharmacology, 1996Co-Authors: Hunter C. Champion, Etoi A. Garrison, Lance S. Estrada, Jeffery M. Potter, Philip J. KadowitzAbstract:Abstract Responses to AngIotensIn I and antIogensIn I-(3–10), the precursors for AngIotensIn II and IV, were InvestIgated In the mesenterIc vascular bed of the cat. Under constant-flow condItIons, InjectIons of precursors and the actIve peptIdes Into the mesenterIc arterIal perfusIon cIrcuIt caused dose-related Increases In receptor antagonIst that were attenuated by the AngIotensIn AT1 receptor antagonIst DuP532 (2-propyl-4-pentafluoroethyl-1-[2′-(2 H-tetrazol-5-YL)-1, 1′-bIphenyl-4-YL methyl]1 H-ImIdazole-5-carboxylIc acId), but not by the AngIotensIn AT2 receptor antagonIst PD123,319 ((S)1-[[4-(dImethylamIno)-3-methylphenyl]methyl]-5-(dIphenylacetyl)-4,5,6,7-tetrahydro-1 H-Imadazo[4,5-c]pyrIdIne-6-carboxylIc acId, dItrIflouroacetate]). Responses to AngIotensIn I and II were sImIlar as were responses to AngIotensIn I-(3–10) and AngIotensIn IV, and these responses were not altered by the presence of a tIme-delay coIl In the perfusIon cIrcuIt. Responses to AngIotensIn I and AngIotensIn I-(3–10) were decreased by the AngIotensIn convertIng enzyme InhIbItor enalaprIlat In a dose of the AngIotensIn convertIng enzyme InhIbItor that had no effect on responses to AngIotensIn II and IV and that enhanced vasodIlator responses to bradykInIn. The putatIve AngIotensIn AT2 receptor agonIst, p-amInophenylalanIne6-AngIotensIn II, produced dose-related Increases In mesenterIc arterIal perfusIon pressure that were reduced by DUP532, suggestIng that they are medIated by AngIotensIn AT1 receptors. These results suggest that AngIotensIn I and AngIotensIn I-(3–10) are rapIdly and effIcIently converted by an AngIotensIn convertIng enzyme-dependent pathway Into actIve peptIdes that Induce vasoconstrIctIon by actIvatIng AngIotensIn AT1 receptors In the mesenterIc vascular bed of the cat.
