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Roger G. Evans - One of the best experts on this subject based on the ideXlab platform.
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An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Yugeesh R. Lankadeva, Roger G. Evans, Junko Kosaka, Clive N. MayAbstract:The development of acute Kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with sepsis, but its pathophysiology remains unclear. Herein, we describe an ovine model of sepsis evoked by the administration of live Escherichia coli in which there is hypotension, peripheral vasodilatation with a large increase in cardiac output; a similar hyperdynamic state to that commonly reported in humans. Interestingly, in this sheep model of sepsis, despite an increase in global Kidney Blood Flow, there is a progressive reduction in renal function. Although renal hyperperfusion develops, renal tissue hypoxia due to redistribution of intrarenal Blood Flow may contribute to the pathogenesis of septic AKI. We have, therefore, developed a novel methodology to chronically implant combination probes to monitor intrarenal tissue perfusion and oxygen tension during the development of septic AKI in conscious sheep with hyperdynamic sepsis.
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prostaglandins and nitric oxide in regional Kidney Blood Flow responses to renal nerve stimulation
Pflügers Archiv: European Journal of Physiology, 2004Co-Authors: Niwanthi W. Rajapakse, Gabriela Alejandra Eppel, Rebecca Lee Flower, Kate M Denton, Simon C Malpas, Roger G. EvansAbstract:We examined the roles of cyclooxygenase products and of interactions between the cyclooxygenase and nitric oxide systems in the mechanisms underlying the relative insensitivity of medullary perfusion to renal nerve stimulation (RNS) in anaesthetized rabbits. To this end we examined the effects of ibuprofen and N(G)-nitro-L: -arginine (L-NNA), both alone and in combination, on the responses of regional Kidney perfusion to RNS. Under control conditions, RNS produced frequency-dependent reductions in total renal Blood Flow (RBF; -82+/-3% at 6 Hz), cortical laser-Doppler flux (CLDF; -84+/-4% at 6 Hz) and, to a lesser extent, medullary laser-Doppler flux (MLDF; -46+/-7% at 6 Hz). Ibuprofen did not affect these responses significantly, suggesting that cyclooxygenase products have little net role in modulating renal vascular responses to RNS. L-NNA enhanced RBF (P=0.002), CLDF (P=0.03) and MLDF (P=0.03) responses to RNS. As we have shown previously, this effect of L-NNA was particularly prominent for MLDF at RNS frequencies < or = 1.5 Hz. Subsequent administration of ibuprofen, in L-NNA-pretreated rabbits, did not affect responses to RNS significantly. We conclude that counter-regulatory actions of NO, but not of prostaglandins, partly underlie the relative insensitivity of medullary perfusion to renal nerve activation.
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α adrenoceptor subtypes mediating regional Kidney Blood Flow responses to renal nerve stimulation
Autonomic Neuroscience: Basic and Clinical, 2004Co-Authors: Gabriela Alejandra Eppel, Leen Lee, Roger G. EvansAbstract:Abstract The mechanisms underlying the relative insensitivity of the renal medullary circulation to renal sympathetic nerve stimulation (RNS) remain unknown. Therefore, we tested the effects of systemic α 1 - and α 2 -adrenoceptor blockade on responses to electrical RNS in pentobarbitone anaesthetized rabbits. Renal Blood Flow (RBF), cortical laser Doppler flux (CLDF), and to a lesser extent medullary LDF (MLDF) were reduced by RNS in a frequency-dependent manner. Prazosin decreased responses of RBF and CLDF, but not MLDF, to RNS. For example, during the control period 4 Hz stimulation reduced RBF, CLDF and MLDF by 85±3%, 89±2%, and 20±12%, respectively, but after prazosin, corresponding responses were 39±3%, 42±5% and 28±7%, respectively. Prazosin markedly blunted pressor and renal vasoconstrictor responses to intravenous phenylephrine, without altering pressor responses to intravenous xylazine. Rauwolscine enhanced renal vasoconstrictor responses to RNS, although this was statistically significant for RBF and CLDF but not MLDF. For example, during the control period 2 Hz stimulation reduced RBF, CLDF and MLDF by 63±7%, 58±7%, and 29±17%, respectively, and after rauwolscine, corresponding responses were 83±4%, 87±1%, and 53±12%, respectively. Rauwolscine markedly blunted renal vasoconstrictor responses to renal arterial guanabenz, but not phenylephrine. These data suggest that α 1 -adrenoceptors contribute to RNS-induced vasoconstriction in the renal cortex, but contribute less in vascular elements controlling medullary perfusion. Activation of α 2 -adrenoceptors appears to blunt RNS-induced renal vasoconstriction, but this mechanism does not underlie the relative insensitivity of medullary perfusion to RNS.
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alpha-Adrenoceptor subtypes mediating regional Kidney Blood Flow responses to renal nerve stimulation.
Autonomic neuroscience : basic & clinical, 2004Co-Authors: Gabriela A Eppel, Leen L Lee, Roger G. EvansAbstract:The mechanisms underlying the relative insensitivity of the renal medullary circulation to renal sympathetic nerve stimulation (RNS) remain unknown. Therefore, we tested the effects of systemic alpha(1)- and alpha(2)-adrenoceptor blockade on responses to electrical RNS in pentobarbitone anaesthetized rabbits. Renal Blood Flow (RBF), cortical laser Doppler flux (CLDF), and to a lesser extent medullary LDF (MLDF) were reduced by RNS in a frequency-dependent manner. Prazosin decreased responses of RBF and CLDF, but not MLDF, to RNS. For example, during the control period 4 Hz stimulation reduced RBF, CLDF and MLDF by 85+/-3%, 89+/-2%, and 20+/-12%, respectively, but after prazosin, corresponding responses were 39+/-3%, 42+/-5% and 28+/-7%, respectively. Prazosin markedly blunted pressor and renal vasoconstrictor responses to intravenous phenylephrine, without altering pressor responses to intravenous xylazine. Rauwolscine enhanced renal vasoconstrictor responses to RNS, although this was statistically significant for RBF and CLDF but not MLDF. For example, during the control period 2 Hz stimulation reduced RBF, CLDF and MLDF by 63+/-7%, 58+/-7%, and 29+/-17%, respectively, and after rauwolscine, corresponding responses were 83+/-4%, 87+/-1%, and 53+/-12%, respectively. Rauwolscine markedly blunted renal vasoconstrictor responses to renal arterial guanabenz, but not phenylephrine. These data suggest that alpha(1)-adrenoceptors contribute to RNS-induced vasoconstriction in the renal cortex, but contribute less in vascular elements controlling medullary perfusion. Activation of alpha(2)-adrenoceptors appears to blunt RNS-induced renal vasoconstriction, but this mechanism does not underlie the relative insensitivity of medullary perfusion to RNS.
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Effect of endothelin-1 on regional Kidney Blood Flow and renal arteriole calibre in rabbits.
Clinical and experimental pharmacology & physiology, 2004Co-Authors: Kate M Denton, Rebecca Lee Flower, Amany Shweta, Leny Finkelstein, Roger G. EvansAbstract:1. Medullary Blood Flow (MBF) is important in the long-term control of arterial pressure. However, it is unclear which vascular elements regulate MBF. 2. Exogenous endothelin (ET)-1 decreases cortical more than medullary Blood Flow. We hypothesized that ET-1 would therefore constrict afferent (AA) and efferent arterioles (EA) of juxtamedullary glomeruli less than those of cortical glomeruli. 3. Mean arterial pressure, renal Blood Flow and cortical (CBF) and medullary (MBF) Blood Flow, via laser-Doppler Flowmetry, were measured before and after intrarenal ET-1 (2 ng/kg per min; n = 6) or vehicle (n = 6) in anaesthetized rabbits. Kidneys were perfusion fixed, vascular casts formed, lumen diameters measured via scanning electron microscopy and relative resistance calculated. 4. Mean arterial pressure was not significantly affected by ET-1 infusion. Cortical glomerular arteriole lumen diameters were significantly reduced in the ET-1-infused group (AA approximately 30%, EA approximately 18%; PA < 0.01), compatible with the decrease in CBF (42 +/- 3%; PGT < 0.01). Juxtamedullary arteriole lumen diameters were also significantly reduced in the ET-1-infused group (AA approximately 34%, EA approximately 21%; PA < 0.01); however, MBF did not decrease. 5. In conclusion, our data suggest that juxtamedullary arterioles are not of primary importance in the regulation of MBF because, despite reductions in juxtamedullary arteriole diameters in response to ET-1, MBF was not decreased.
A G Correia - One of the best experts on this subject based on the ideXlab platform.
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Effects of activation of vasopressin-V1-receptors on regional Kidney Blood Flow and glomerular arteriole diameters.
Journal of Hypertension, 2001Co-Authors: A G Correia, Kate M Denton, Roger G. EvansAbstract:Objectives We tested whether vasoconstriction of juxtamedullary glomerular arterioles contributes to vasopressin V 1 -receptor-mediated reductions in medullary perfusion (MBF). Design and methods The left Kidney of pentobarbitone anaesthetized rabbits was denervated, a perivascular Flow probe placed around the renal artery and laser-Doppler Flow probes positioned in the inner medulla and on the cortical surface. Rabbits then received a 30 min intravenous infusion of [Phe 2 ,Ile 3 ,Orn 8 ]vasopressin (V 1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n = 7). Kidneys were perfusion fixed at the final recorded mean arterial pressure (MAP) and filled with methacrylate casting material. Diameters of afferent and efferent arterioles were determined by scanning electron microscopy. Results V 1 -AG increased MAP (19 ± 3%) and reduced MBF (30 ± 8%) but not cortical perfusion or total renal Blood Flow. Vehicle-treatment did not significantly affect these variables. After vehicle- and V 1 -AG-treatment, juxtamedullary afferent arteriole luminal diameter averaged 15.35 ± 1.31 and 15.88 ± 1.86 pm, respectively (P = 0.92), while juxtamedullary efferent arteriole luminal diameter averaged 17.75 ± 1.86 and 18.36 ± 2.24 μm, respectively (P= 0.93). Conclusions V 1 -AG reduced MBF but did not significantly affect juxtamedullary arteriolar diameter. Our results therefore do not support a role for juxtamedullary arterioles in producing V 1 -receptor-mediated reductions in MBF, suggesting that downstream vascular elements (e.g. outer medullary descending vasa recta) might be involved.
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Effects of activation of vasopressin-V1-receptors on regional Kidney Blood Flow and glomerular arteriole diameters.
Journal of hypertension, 2001Co-Authors: A G Correia, K M Denton, R G EvansAbstract:We tested whether vasoconstriction of juxtamedullary glomerular arterioles contributes to vasopressin V1 -receptor-mediated reductions in medullary perfusion (MBF). The left Kidney of pentobarbitone anaesthetized rabbits was denervated, a perivascular Flow probe placed around the renal artery and laser-Doppler Flow probes positioned in the inner medulla and on the cortical surface. Rabbits then received a 30 min intravenous infusion of [Phe2,Ile3,Orn8]vasopressin (V1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n = 7). Kidneys were perfusion fixed at the final recorded mean arterial pressure (MAP) and filled with methacrylate casting material. Diameters of afferent and efferent arterioles were determined by scanning electron microscopy. V1 -AG increased MAP (19 +/- 3%) and reduced MBF (30 +/- 8%) but not cortical perfusion or total renal Blood Flow. Vehicle-treatment did not significantly affect these variables. After vehicle- and V1-AG-treatment, juxtamedullary afferent arteriole luminal diameter averaged 15.35 +/- 1.31 and 15.88 +/- 1.86 microm, respectively (P= 0.92), while juxtamedullary efferent arteriole luminal diameter averaged 17.75 +/- 1.86 and 18.36 +/- 2.24 microm, respectively (P= 0.93). V1-AG reduced MBF but did not significantly affect juxtamedullary arteriolar diameter. Our results therefore do not support a role for juxtamedullary arterioles in producing V1-receptor-mediated reductions in MBF, suggesting that downstream vascular elements (e.g. outer medullary descending vasa recta) might be involved.
Kate M Denton - One of the best experts on this subject based on the ideXlab platform.
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prostaglandins and nitric oxide in regional Kidney Blood Flow responses to renal nerve stimulation
Pflügers Archiv: European Journal of Physiology, 2004Co-Authors: Niwanthi W. Rajapakse, Gabriela Alejandra Eppel, Rebecca Lee Flower, Kate M Denton, Simon C Malpas, Roger G. EvansAbstract:We examined the roles of cyclooxygenase products and of interactions between the cyclooxygenase and nitric oxide systems in the mechanisms underlying the relative insensitivity of medullary perfusion to renal nerve stimulation (RNS) in anaesthetized rabbits. To this end we examined the effects of ibuprofen and N(G)-nitro-L: -arginine (L-NNA), both alone and in combination, on the responses of regional Kidney perfusion to RNS. Under control conditions, RNS produced frequency-dependent reductions in total renal Blood Flow (RBF; -82+/-3% at 6 Hz), cortical laser-Doppler flux (CLDF; -84+/-4% at 6 Hz) and, to a lesser extent, medullary laser-Doppler flux (MLDF; -46+/-7% at 6 Hz). Ibuprofen did not affect these responses significantly, suggesting that cyclooxygenase products have little net role in modulating renal vascular responses to RNS. L-NNA enhanced RBF (P=0.002), CLDF (P=0.03) and MLDF (P=0.03) responses to RNS. As we have shown previously, this effect of L-NNA was particularly prominent for MLDF at RNS frequencies < or = 1.5 Hz. Subsequent administration of ibuprofen, in L-NNA-pretreated rabbits, did not affect responses to RNS significantly. We conclude that counter-regulatory actions of NO, but not of prostaglandins, partly underlie the relative insensitivity of medullary perfusion to renal nerve activation.
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Effect of endothelin-1 on regional Kidney Blood Flow and renal arteriole calibre in rabbits.
Clinical and experimental pharmacology & physiology, 2004Co-Authors: Kate M Denton, Rebecca Lee Flower, Amany Shweta, Leny Finkelstein, Roger G. EvansAbstract:1. Medullary Blood Flow (MBF) is important in the long-term control of arterial pressure. However, it is unclear which vascular elements regulate MBF. 2. Exogenous endothelin (ET)-1 decreases cortical more than medullary Blood Flow. We hypothesized that ET-1 would therefore constrict afferent (AA) and efferent arterioles (EA) of juxtamedullary glomeruli less than those of cortical glomeruli. 3. Mean arterial pressure, renal Blood Flow and cortical (CBF) and medullary (MBF) Blood Flow, via laser-Doppler Flowmetry, were measured before and after intrarenal ET-1 (2 ng/kg per min; n = 6) or vehicle (n = 6) in anaesthetized rabbits. Kidneys were perfusion fixed, vascular casts formed, lumen diameters measured via scanning electron microscopy and relative resistance calculated. 4. Mean arterial pressure was not significantly affected by ET-1 infusion. Cortical glomerular arteriole lumen diameters were significantly reduced in the ET-1-infused group (AA approximately 30%, EA approximately 18%; PA < 0.01), compatible with the decrease in CBF (42 +/- 3%; PGT < 0.01). Juxtamedullary arteriole lumen diameters were also significantly reduced in the ET-1-infused group (AA approximately 34%, EA approximately 21%; PA < 0.01); however, MBF did not decrease. 5. In conclusion, our data suggest that juxtamedullary arterioles are not of primary importance in the regulation of MBF because, despite reductions in juxtamedullary arteriole diameters in response to ET-1, MBF was not decreased.
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Effects of activation of vasopressin-V1-receptors on regional Kidney Blood Flow and glomerular arteriole diameters.
Journal of Hypertension, 2001Co-Authors: A G Correia, Kate M Denton, Roger G. EvansAbstract:Objectives We tested whether vasoconstriction of juxtamedullary glomerular arterioles contributes to vasopressin V 1 -receptor-mediated reductions in medullary perfusion (MBF). Design and methods The left Kidney of pentobarbitone anaesthetized rabbits was denervated, a perivascular Flow probe placed around the renal artery and laser-Doppler Flow probes positioned in the inner medulla and on the cortical surface. Rabbits then received a 30 min intravenous infusion of [Phe 2 ,Ile 3 ,Orn 8 ]vasopressin (V 1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n = 7). Kidneys were perfusion fixed at the final recorded mean arterial pressure (MAP) and filled with methacrylate casting material. Diameters of afferent and efferent arterioles were determined by scanning electron microscopy. Results V 1 -AG increased MAP (19 ± 3%) and reduced MBF (30 ± 8%) but not cortical perfusion or total renal Blood Flow. Vehicle-treatment did not significantly affect these variables. After vehicle- and V 1 -AG-treatment, juxtamedullary afferent arteriole luminal diameter averaged 15.35 ± 1.31 and 15.88 ± 1.86 pm, respectively (P = 0.92), while juxtamedullary efferent arteriole luminal diameter averaged 17.75 ± 1.86 and 18.36 ± 2.24 μm, respectively (P= 0.93). Conclusions V 1 -AG reduced MBF but did not significantly affect juxtamedullary arteriolar diameter. Our results therefore do not support a role for juxtamedullary arterioles in producing V 1 -receptor-mediated reductions in MBF, suggesting that downstream vascular elements (e.g. outer medullary descending vasa recta) might be involved.
R G Evans - One of the best experts on this subject based on the ideXlab platform.
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Effects of activation of vasopressin-V1-receptors on regional Kidney Blood Flow and glomerular arteriole diameters.
Journal of hypertension, 2001Co-Authors: A G Correia, K M Denton, R G EvansAbstract:We tested whether vasoconstriction of juxtamedullary glomerular arterioles contributes to vasopressin V1 -receptor-mediated reductions in medullary perfusion (MBF). The left Kidney of pentobarbitone anaesthetized rabbits was denervated, a perivascular Flow probe placed around the renal artery and laser-Doppler Flow probes positioned in the inner medulla and on the cortical surface. Rabbits then received a 30 min intravenous infusion of [Phe2,Ile3,Orn8]vasopressin (V1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n = 7). Kidneys were perfusion fixed at the final recorded mean arterial pressure (MAP) and filled with methacrylate casting material. Diameters of afferent and efferent arterioles were determined by scanning electron microscopy. V1 -AG increased MAP (19 +/- 3%) and reduced MBF (30 +/- 8%) but not cortical perfusion or total renal Blood Flow. Vehicle-treatment did not significantly affect these variables. After vehicle- and V1-AG-treatment, juxtamedullary afferent arteriole luminal diameter averaged 15.35 +/- 1.31 and 15.88 +/- 1.86 microm, respectively (P= 0.92), while juxtamedullary efferent arteriole luminal diameter averaged 17.75 +/- 1.86 and 18.36 +/- 2.24 microm, respectively (P= 0.93). V1-AG reduced MBF but did not significantly affect juxtamedullary arteriolar diameter. Our results therefore do not support a role for juxtamedullary arterioles in producing V1-receptor-mediated reductions in MBF, suggesting that downstream vascular elements (e.g. outer medullary descending vasa recta) might be involved.
Niwanthi W. Rajapakse - One of the best experts on this subject based on the ideXlab platform.
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prostaglandins and nitric oxide in regional Kidney Blood Flow responses to renal nerve stimulation
Pflügers Archiv: European Journal of Physiology, 2004Co-Authors: Niwanthi W. Rajapakse, Gabriela Alejandra Eppel, Rebecca Lee Flower, Kate M Denton, Simon C Malpas, Roger G. EvansAbstract:We examined the roles of cyclooxygenase products and of interactions between the cyclooxygenase and nitric oxide systems in the mechanisms underlying the relative insensitivity of medullary perfusion to renal nerve stimulation (RNS) in anaesthetized rabbits. To this end we examined the effects of ibuprofen and N(G)-nitro-L: -arginine (L-NNA), both alone and in combination, on the responses of regional Kidney perfusion to RNS. Under control conditions, RNS produced frequency-dependent reductions in total renal Blood Flow (RBF; -82+/-3% at 6 Hz), cortical laser-Doppler flux (CLDF; -84+/-4% at 6 Hz) and, to a lesser extent, medullary laser-Doppler flux (MLDF; -46+/-7% at 6 Hz). Ibuprofen did not affect these responses significantly, suggesting that cyclooxygenase products have little net role in modulating renal vascular responses to RNS. L-NNA enhanced RBF (P=0.002), CLDF (P=0.03) and MLDF (P=0.03) responses to RNS. As we have shown previously, this effect of L-NNA was particularly prominent for MLDF at RNS frequencies < or = 1.5 Hz. Subsequent administration of ibuprofen, in L-NNA-pretreated rabbits, did not affect responses to RNS significantly. We conclude that counter-regulatory actions of NO, but not of prostaglandins, partly underlie the relative insensitivity of medullary perfusion to renal nerve activation.
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Lipoxygenase and cyclo-oxygenase products in the control of regional Kidney Blood Flow in rabbits
Clinical and experimental pharmacology & physiology, 2003Co-Authors: Jeremy James Oliver, Niwanthi W. Rajapakse, Gabriela Alejandra Eppel, Roger G. EvansAbstract:1. The aim of the present study was to examine the roles of cyclo-oxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonate signalling cascades in the control of regional Kidney Blood Flow. 2. In pentobarbitone-anaesthetized rabbits treated with NG-nitro-l-arginine and glyceryl trinitrate to 'clamp' nitric oxide, we determined the effects of ibuprofen (a COX inhibitor) and esculetin (a LOX inhibitor) on resting systemic and renal haemodynamics and responses to renal arterial infusions of vasoconstrictors. 3. Ibuprofen increased mean arterial pressure (14 +/- 5%) and reduced medullary laser Doppler flux (MLDF; 26 +/- 6%) when administered with esculetin. A similar pattern of responses was observed when ibuprofen was given alone, although the reduction in MLDF was not statistically significant. Esculetin tended to increase renal Blood Flow (RBF; 16 +/- 7%) and MLDF (28 +/- 13%) when given alone, but not when combined with ibuprofen. 4. After vehicle, renal arterial infusions of noradrenaline, angiotensin II and endothelin-1 reduced RBF and cortical laser Doppler flux (CLDF), but not MLDF. In contrast, renal arterial [Phe2,Ile3,Orn8]-vasopressin reduced MLDF but not RBF or CLDF. Ibuprofen alone did not significantly affect these responses. Esculetin, when given alone, but not when combined with ibuprofen, enhanced noradrenaline-induced renal vasoconstriction. In contrast, esculetin did not significantly affect responses to [Phe2,Ile3,Orn8]-vasopressin, angiotensin II or endothelin-1. 5. We conclude that COX products contribute to the maintenance of arterial pressure and renal medullary perfusion under 'nitric oxide clamp' conditions, but not to renal haemodynamic responses to the vasoconstrictors we tested. Lipoxygenase products may blunt noradrenaline-induced vasoconstriction, but our observations may, instead, reflect LOX-independent effects of esculetin.
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Nitric oxide in responses of regional Kidney Blood Flow to vasoactive agents in anesthetized rabbits.
Journal of cardiovascular pharmacology, 2002Co-Authors: Niwanthi W. Rajapakse, Jeremy James Oliver, Roger G. EvansAbstract:To determine whether differential release of nitric oxide underlies the diversity of regional Kidney Blood Flow responses to vasoactive agents, this study examined how nitric oxide synthase blockade with IV N G -nitro-L-arginine (L-NNA), and also IV L-NNA plus co-infusion of glyceryl trinitrate, affected responses to renal arterial boluses and infusions of vasoactive agents. L-NNA, but not vehicle, or L-NNA plus glyceryl trinitrate, increased mean arterial pressure (35%) and reduced renal Blood Flow (20%), cortical perfusion (11%), and medullary perfusion (54%). L-NNA plus glyceryl trinitrate, but not L-NNA alone, blunted renal vasodilatation in response to boluses of bradykinin and acetylcholine, abolished increased medullary perfusion after bolus angiotensin II, and enhanced reductions in medullary perfusion, and to a lesser extent those in renal Blood Flow and cortical perfusion, during norepinephrine infusion. Neither L-NNA, nor L-NNA plus glyceryl trinitrate, affected responses to infusions of angiotensin II, [Phe 2 ,Ile 3 ,Orn 8 ]-vasopressin, or endothelin-1. The data indicate roles for nitric oxide in angiotensin II-induced increases in medullary perfusion and in protecting medullary perfusion from norepinephrine-induced vasoconstriction. However, differential engagement of nitric oxide synthase cannot completely account for the diversity of responses of regional Kidney perfusion to vasoactive agents. Effects of nitric oxide synthase blockade on renal vascular responses to vasoactive agents were revealed only when glyceryl trinitrate was co-infused to restore resting nitrergic vasodilator tone. This may reflect interactions between nitric oxide and other vasodilator mediators, in modulating renal hemodynamic responses to vasoactive agents.
