The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Catherine C.y. Pang - One of the best experts on this subject based on the ideXlab platform.
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Effects of nimesulide, a selective COX-2 inhibitor, on cardiovascular function in 2 rat models of diabetes.
Journal of cardiovascular pharmacology, 2014Co-Authors: Joanne Y.t. Leung, Catherine C.y. PangAbstract:Cyclooxygenase-2 (COX-2) has been found to be activated in diabetes. We investigated whether nimesulide (selective COX-2 inhibitor) alters cardiovascular responses to adrenaline in 2 rat models of diabetes. Wistar rats (5-week old) were continuously fed a normal or high-fructose diet (60% of caloric intake). At week 2, half of the rats in each diet regimen were given streptozotocin (STZ) (60 mg/kg, intravenously). At week 6, cardiovascular effects of adrenaline (6 and 16 × 10 mol·kg·min, intravenously) were measured in 4 groups of Thiobutabarbital-anesthetized rats (control, fructose, STZ, and fructose-streptozotocin [F-STZ]) before and after the injection of nimesulide (3 mg/kg, intravenously). Both the STZ and F-STZ groups exhibited hyperglycemia and significantly (P < 0.05) reduced left ventricular contractility, mean arterial pressure, arterial and venous resistance, and mean circulatory filling pressure (index of venous tone) responses to adrenaline, relative to the control and fructose groups. Nimesulide did not affect responses in the control and fructose groups but increased the venous and, to a less extent, arterial constriction to adrenaline in both the groups of diabetic rats. The cardiac contractile responses, however, were not altered after nimesulide treatment. The results show that nimesulide partially restored arterial and venous constriction to adrenaline in rats with STZ- and F-STZ-induced diabetes.
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Differential constrictor responses of cephalic and caudal vasculature to α-adrenoceptor agonist after hind limb unloading
Canadian journal of physiology and pharmacology, 2010Co-Authors: Simon R. Hutchings, Jong Moo Kimj.m. Kim, Dongzhe Songd. Song, Catherine C.y. PangAbstract:We examined the effects of hind limb unloading (HLU, 14 days) on constriction of carotid and iliac arterial beds in vivo in Thiobutabarbital-anaesthetized rats and isolated carotid and iliac arteries in vitro. Both control and HLU rats had similar arterial pressure and carotid and iliac arterial flows. The HLU rats had increased carotid arterial but reduced iliac arterial constriction in response to methoxamine (α1-adrenoceptor agonist) in vivo. In contrast, constriction in response to methoxamine was reduced in the isolated carotid and unchanged in the iliac artery of HLU rats relative to control rats. Thus, HLU is associated with increased constriction of carotid arterial bed but reduced constriction of the isolated carotid artery, and reduced constriction of iliac arterial bed but unchanged constriction of the isolated iliac artery. These results show differential influence of HLU on constriction of cephalic and caudal arterial beds, and differential effect on constrictions of arterial beds relative to conduit arteries.
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Altered vasodilator role of nitric oxide synthase in the pancreas, heart and brain of rats with spontaneous type 2 diabetes.
European journal of pharmacology, 2008Co-Authors: Dongzhe Song, Reina Yao, Catherine C.y. PangAbstract:Type 2 diabetes is associated with altered regional blood flow and expression of nitric oxide synthase (NOS). We examined the functional role of constitutive and inducible NOS synthase (cNOS and iNOS, respectively) on regional blood flow in Thiobutabarbital-anesthetized Zucker diabetic fatty (ZDF) and control rats via the radioactive microspheres technique. Blood flow was measured at baseline (1 h after surgery), after i.v. administration of 1400W (N-3-aminomethyl-benzyl-acetamidine, selective iNOS inhibitor, 3 mg/kg), and again after i.v. N(G)-nitro-l-arginine methyl ester (L-NAME, non-selective NOS inhibitor, 8 mg/kg). Both groups had similar baseline mean arterial pressure, cardiac output and total peripheral resistance, but the ZDF rats had lower heart rate relative to the control rats (272 versus 305 beats/min). Whereas 1400W did not alter mean arterial pressure or blood flow in either group, L-NAME markedly increased mean arterial pressure and total peripheral resistance, and reduced cardiac output, heart rate, blood flow and arterial conductance in all organs/tissues of both the control and ZDF rats. L-NAME caused greater vasoconstriction in the heart (1.5-times the constriction in control rats) and brain (1.5-times) of the ZDF rats, but less in the pancreas (0.6-times). Thus, cNOS had greater vasodilator control of the heart and brain, but less in the pancreas of the ZDF than control rats. iNOS has negligible influence on blood flow in both groups of rats.
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Possible mechanism of the vasodepressor effect of endokinin a/b in anesthetized rats.
Journal of cardiovascular pharmacology, 2005Co-Authors: Aly M. Abdelrahman, Harley T. Syyong, Anindita A.g. Tjahjadi, Catherine C.y. PangAbstract:We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in Thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with N G -nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), methylene blue (inhibitor of soluble guanylyl cyclase), indomethacin (cyclooxygenase inhibitor), or tetraethylammonium (TEA, nonspecific K + channel blocker). L-NAME reduced the half-recovery time of the vasodepressor effect of endokinin A/B relative to responses in rats pretreated with either saline or norepinephrine, which caused a similar pressor effect as did L-NAME. Methylene blue, but not TEA or indomethacin, reduced the recovery time of the vasodepressor effect of endokinin A/B. Therefore, the vasodepressor effect of endokinin A/B is mediated via the nitric oxide/L-arginine pathway and activation of soluble guanylyl cyclase but not by production of prostanoids or opening of TEA-sensitive K + channels.
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Analysis of the mechanism of the vasodepressor effect of urocortin in anesthetized rats.
Pharmacology, 2004Co-Authors: Aly M. Abdelrahman, Harley T. Syyong, Anindita A.g. Tjahjadi, Catherine C.y. PangAbstract:The aim was to examine if the depressor effect of urocortin involves activation of the nitric oxide (NO)/L-arginine pathway, production of prostanoids or opening of K(+)-channels. I. v. bolus urocortin (0.1-3 nmol/kg) dose-dependently decreased mean arterial pressure in Thiobutabarbital-anesthetized rats. The depressor effect of urocortin was unaffected by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, inhibitor of NO synthase, i.v. bolus) or noradrenaline (i.v. infusion), which increased arterial pressure to a similar level as that produced by L-NAME. In addition, methylene blue (inhibitor of soluble guanylyl cyclase, i.v. infusion), indomethacin (cyclooxygenase inhibitor, i.v. bolus), glibenclamide (blocker of ATP-sensitive K(+)-channels, i.v. bolus) or tetraethylammonium (a non specific K(+)-channel blocker, i.v. bolus) did not affect the depressor effect of urocortin. In conclusion, the depressor effect of urocortin in anesthetized rats is not mediated via the NO/L-arginine pathway, activation of soluble guanylyl cyclase, production of prostanoids, opening of TEA sensitive K(+)-channels nor opening of ATP sensitive K(+)-channels.
Aly M. Abdelrahman - One of the best experts on this subject based on the ideXlab platform.
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Possible mechanism of the vasodepressor effect of endokinin a/b in anesthetized rats.
Journal of cardiovascular pharmacology, 2005Co-Authors: Aly M. Abdelrahman, Harley T. Syyong, Anindita A.g. Tjahjadi, Catherine C.y. PangAbstract:We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in Thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with N G -nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), methylene blue (inhibitor of soluble guanylyl cyclase), indomethacin (cyclooxygenase inhibitor), or tetraethylammonium (TEA, nonspecific K + channel blocker). L-NAME reduced the half-recovery time of the vasodepressor effect of endokinin A/B relative to responses in rats pretreated with either saline or norepinephrine, which caused a similar pressor effect as did L-NAME. Methylene blue, but not TEA or indomethacin, reduced the recovery time of the vasodepressor effect of endokinin A/B. Therefore, the vasodepressor effect of endokinin A/B is mediated via the nitric oxide/L-arginine pathway and activation of soluble guanylyl cyclase but not by production of prostanoids or opening of TEA-sensitive K + channels.
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Analysis of the mechanism of the vasodepressor effect of urocortin in anesthetized rats.
Pharmacology, 2004Co-Authors: Aly M. Abdelrahman, Harley T. Syyong, Anindita A.g. Tjahjadi, Catherine C.y. PangAbstract:The aim was to examine if the depressor effect of urocortin involves activation of the nitric oxide (NO)/L-arginine pathway, production of prostanoids or opening of K(+)-channels. I. v. bolus urocortin (0.1-3 nmol/kg) dose-dependently decreased mean arterial pressure in Thiobutabarbital-anesthetized rats. The depressor effect of urocortin was unaffected by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, inhibitor of NO synthase, i.v. bolus) or noradrenaline (i.v. infusion), which increased arterial pressure to a similar level as that produced by L-NAME. In addition, methylene blue (inhibitor of soluble guanylyl cyclase, i.v. infusion), indomethacin (cyclooxygenase inhibitor, i.v. bolus), glibenclamide (blocker of ATP-sensitive K(+)-channels, i.v. bolus) or tetraethylammonium (a non specific K(+)-channel blocker, i.v. bolus) did not affect the depressor effect of urocortin. In conclusion, the depressor effect of urocortin in anesthetized rats is not mediated via the NO/L-arginine pathway, activation of soluble guanylyl cyclase, production of prostanoids, opening of TEA sensitive K(+)-channels nor opening of ATP sensitive K(+)-channels.
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Regional haemodynamic effects of urocortin in the anaesthetized rat.
European journal of pharmacology, 2003Co-Authors: Aly M. Abdelrahman, Catherine C.y. PangAbstract:Urocortin is an endogenous vasodilator peptide that is related to corticotrophin-releasing factor. We examined the haemodynamic effects of urocortin in Thiobutabarbital-anaesthetized rats, via the triple-isotope microspheres technique. Urocortin (3 nmol/kg, i.v. bolus) reduced mean arterial pressure (-25 mm Hg) through a decrease in total peripheral resistance (-43%). This was associated with an increase in cardiac output (+24%) and vasodilatation of the following tissues: heart and stomach (approximately 300% of baseline); liver, intestine, caecum/colon, skeletal muscle and skin (approximately 200%); and testes (approximately 150%). Arterial conductances of the kidneys, spleen and brain were unaffected by urocortin. Neither the vehicle (0.9% NaCl) nor a low dose of urocortin (0.3 nmol/kg) altered any measurements. Therefore, urocortin causes generalized vasodilatation as follows: heart and stomach>liver, intestine, caecum/colon, skeletal muscle and skin>testes.
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Regional hemodynamic effects of nociceptin/orphanin FQ in the anesthetized rat
European journal of pharmacology, 2002Co-Authors: Aly M. Abdelrahman, Catherine C.y. PangAbstract:Abstract This study examined the vasodilator action of nociceptin, an endogenous opioid receptor-like ligand (ORL1), in Thiobutabarbital-anesthetized rats, via the triple-isotope microspheres technique. Nociceptin (10, 30 nmol/kg, left ventricular injection) reduced mean arterial pressure (−27, −29 mm Hg), total peripheral resistance (−36, −41% of baseline) and heart rate (−8, −11% of baseline), but did not significantly affect cardiac output. The vehicle (0.9% NaCl) did not alter hemodynamics. Both doses of nociceptin caused similar changes in arterial flow and conductance of all tissues. Nociceptin increased flows to the skeletal muscle, slightly reduced flows to the caecum and colon, but did not alter flows to other organs and tissues. With flow normalized by pressure to reflect intrinsic vascular tone, nociceptin was found to increase arterial conductance of all tissues, except for the intestine, spleen, caecum and colon. Its dilator influence was greater in the skeletal muscle (≈250% of baseline conductance) than the lungs, heart, liver, stomach, kidneys, skin, testes and brain (140–160% of baseline). Thus, nociceptin causes generalized vasodilatation; its greatest influence is on the skeletal muscle bed.
K B Brosnihan - One of the best experts on this subject based on the ideXlab platform.
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The angiotensin II AT1 receptor antagonist irbesartan prevents thromboxane A2-induced vasoconstriction in the rat hind-limb vascular bed in vivo.
Journal of Hypertension, 2001Co-Authors: M Fukuhara, L A Neves, D I Diz, C M Ferrario, K B BrosnihanAbstract:Objective We studied the vasoconstrictor effects of the thromboxane A 2 (TxA 2 ) analogue U46619 in the perfused hind limb of rats under constant flow before and after intravenous injection of irbesartan, an angiotensin II AT 1 receptor antagonist, to test whether irbesartan interacts in vivo with the thromboxane A 2 /prostaglandin endoperoxidase H 2 (TxA 2 /PGH 2 ) receptor. Design Male Sprague-Dawley rats (n = 15, body weight 350-420 g) were anesthetized with Thiobutabarbital sodium (Inactin, 100 mg/kg intraperitoneally). Regional vascular responses to U46619 (0.5 and 1.0 μg) were investigated in the rat hind quarter under conditions of controlled flow before and after administration of irbesartan (10 mg/kg, intravenously). In addition, to test the specificity of the effect of irbesartan on U46619, phenylephrine (0.5, 1.0 μg) and another AT 1 receptor antagonist, candesartan CV11974 (0.3 mg/kg, intravenously) were used. Results The dose-dependent increases in hind-limb perfusion pressure produced by U46619 were significantly attenuated by prior injection of irbesartan, at a dose that blocked the angiotensin II (Ang II) pressor responses. The specificity for the response was shown with the demonstrations that the increase in vascular resistance produced by phenylephrine was unchanged by irbesartan and, furthermore, that the increase in vascular resistance produced by U46619 was unchanged by another AT 1 receptor antagonist, candesartan. Conclusion This study demonstrates that irbesartan interacts at the TxA 2 /PGH 2 receptor in the rat's hind limb in vivo, to modify changes in local regional vascular resistance. The dual antagonistic actions of irbesartan, acting at both AT 1 and TxA 2 receptors in blood vessels, may overall enhance its therapeutic profile in the treatment of hypertension.
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The angiotensin II AT1 receptor antagonist irbesartan prevents thromboxane A2-induced vasoconstriction in the rat hind-limb vascular bed in vivo.
Journal of hypertension, 2001Co-Authors: M Fukuhara, L A Neves, D I Diz, C M Ferrario, K B BrosnihanAbstract:We studied the vasoconstrictor effects of the thromboxane A2 (TxA2) analogue U46619 in the perfused hind limb of rats under constant flow before and after intravenous injection of irbesartan, an angiotensin II AT1 receptor antagonist, to test whether irbesartan interacts in vivo with the thromboxane A2/prostaglandin endoperoxidase H2 (TxA2/PGH2) receptor. Male Sprague-Dawley rats (n = 15, body weight 350-420 g) were anesthetized with Thiobutabarbital sodium (Inactin, 100 mg/kg intraperitoneally). Regional vascular responses to U46619 (0.5 and 1.0 microg) were investigated in the rat hind quarter under conditions of controlled flow before and after administration of irbesartan (10 mg/kg, intravenously). In addition, to test the specificity of the effect of irbesartan on U46619, phenylephrine (0.5, 1.0 microg) and another AT1 receptor antagonist, candesartan CV11974 (0.3 mg/kg, intravenously) were used. The dose-dependent increases in hind-limb perfusion pressure produced by U46619 were significantly attenuated by prior injection of irbesartan, at a dose that blocked the angiotensin II (Ang II) pressor responses. The specificity for the response was shown with the demonstrations that the increase in vascular resistance produced by phenylephrine was unchanged by irbesartan and, furthermore, that the increase in vascular resistance produced by U46619 was unchanged by another AT1 receptor antagonist, candesartan. This study demonstrates that irbesartan interacts at the TxA2/PGH2 receptor in the rat's hind limb in vivo, to modify changes in local regional vascular resistance. The dual antagonistic actions of irbesartan, acting at both AT1 and TxA2 receptors in blood vessels, may overall enhance its therapeutic profile in the treatment of hypertension.
Volker Vallon - One of the best experts on this subject based on the ideXlab platform.
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Kidney function in mice: Thiobutabarbital versus α-chloralose anesthesia
Naunyn-Schmiedeberg's Archives of Pharmacology, 2004Co-Authors: Timo Rieg, K Richter, Hartmut Osswald, Volker VallonAbstract:Mice that lack or over-express a gene of interest are important tools for unraveling gene function. The determination of single nephron function by micropuncture or precise determination of glomerular filtration rate (GFR) by inulin clearance method require experiments under anesthesia. A good anesthetic protocol should allow for reasonable and stable glomerular and tubular function. The aim of this study was to compare the commonly used Thiobutabarbital (TBB) versus α-chloralose (CHL) anesthesia with regard to absolute levels and the stability of blood pressure, heart rate, and kidney function. Male CD1 mice were anesthetized with TBB (100 mg/kg body weight i.p.) or CHL (120 mg/kg body weight i.p.), plus ketamine (100 mg/kg body weight i.m.) given to every mouse for analgesia. After preparation for clearance experiments, two 30-min urine collections were performed at periods 1 and 2 (P1 and P2). It was observed that heart rate and mean arterial blood pressure did not differ between TBB ( n =9) vs. CHL ( n =9) and were stable through P1 and P2. In CHL, GFR as well as fractional excretion of fluid, Na^+ and K^+ were stable from P1 to P2 (P1: 190±15 μl/min, 1.6±0.2%, 0.7±0.1%, 35±5%; percent change in P2: 1±6, 26±10, 29±15, 6±10 respectively). In TBB, GFR was significantly greater vs. CHL in P1 and did not significantly change in P2 (246±8 μl/min, p
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kidney function in mice Thiobutabarbital versus α chloralose anesthesia
Naunyn-schmiedebergs Archives of Pharmacology, 2004Co-Authors: Timo Rieg, K Richter, Hartmut Osswald, Volker VallonAbstract:Mice that lack or over-express a gene of interest are important tools for unraveling gene function. The determination of single nephron function by micropuncture or precise determination of glomerular filtration rate (GFR) by inulin clearance method require experiments under anesthesia. A good anesthetic protocol should allow for reasonable and stable glomerular and tubular function. The aim of this study was to compare the commonly used Thiobutabarbital (TBB) versus alpha-chloralose (CHL) anesthesia with regard to absolute levels and the stability of blood pressure, heart rate, and kidney function. Male CD1 mice were anesthetized with TBB (100 mg/kg body weight i.p.) or CHL (120 mg/kg body weight i.p.), plus ketamine (100 mg/kg body weight i.m.) given to every mouse for analgesia. After preparation for clearance experiments, two 30-min urine collections were performed at periods 1 and 2 (P1 and P2). It was observed that heart rate and mean arterial blood pressure did not differ between TBB ( n=9) vs. CHL ( n=9) and were stable through P1 and P2. In CHL, GFR as well as fractional excretion of fluid, Na(+) and K(+) were stable from P1 to P2 (P1: 190+/-15 microl/min, 1.6+/-0.2%, 0.7+/-0.1%, 35+/-5%; percent change in P2: 1+/-6, 26+/-10, 29+/-15, 6+/-10 respectively). In TBB, GFR was significantly greater vs. CHL in P1 and did not significantly change in P2 (246+/-8 microl/min, p<0.05; percent change: -6.5+/-4). Fractional excretion of fluid, Na(+) and K(+) were not significantly different vs. CHL in P1, but significantly increased in P2 (P1: 1.5+/-0.2%, 1.1+/-0.2%, 31+/-3%; percent change in P2: 122+/-23, 128+/-21 and 29+/-6 respectively; each p<0.05 vs. P1). In conclusion, mice under both anesthetic regimens present reasonable and stable blood pressure and reasonable kidney function, but kidney reabsorption is more stable under CHL than under TBB anesthesia, which may facilitate study of the response in kidney function to acute interventions.
Roger G. Evans - One of the best experts on this subject based on the ideXlab platform.
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AT2 receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension
British journal of pharmacology, 2005Co-Authors: Lisa Michelle Duke, Robert E Widdop, Michelle M Kett, Roger G. EvansAbstract:1. Renal medullary blood flow is relatively insensitive to angiotensin II (Ang II)-induced vasoconstriction, due partly to AT(1)-mediated release of nitric oxide and/or prostaglandins. AT(2)-receptor activation appears to blunt AT(1)-mediated vasodilatation within the medullary circulation. This could affect long-term efficacy of antihypertensive pharmacotherapies targeting the renin/angiotensin system, particularly in Ang II-dependent forms of hypertension. 2. We tested the effects of AT(1)- and AT(2)-receptor blockade on basal cortical and medullary laser Doppler flux (CLDF and MLDF), and on responses to renal arterial infusion of Ang II, in rats with 2 kidney, 1 clip (2K1C) hypertension and sham-operated controls. Studies were carried out in Thiobutabarbital (175 mg kg(-1), i.p.) anaesthetised rats, 4 weeks after clipping, or sham surgery (n=6 in each of eight groups). 3. Candesartan (10 microg kg(-1) h(-1), intravenous (i.v.)) reduced mean arterial pressure ( approximately 17%) and increased CLDF ( approximately 24%), similarly in both sham and 2K1C rats, but did not significantly affect MLDF. PD123319 (1 mg kg(-1) h(-1), i.v.) increased basal MLDF (19%) in 2K1C but not sham rats, without significantly affecting other variables. 4. In sham rats, renal arterial infusion of Ang II (1-100 ng kg(-1) min(-1)) dose dependently decreased CLDF (up to 44%), but did not significantly affect MLDF. These effects were markedly blunted in 2K1C rats. After PD123319, Ang II dose dependently increased MLDF (up to 38%) in sham but not 2K1C rats. Candesartan abolished all effects of Ang II, including those seen after PD123319. 5. Our data indicate that AT(1) receptors mediate medullary vasodilatation, which is opposed by AT(2)-receptor activation. In 2K1C hypertension, AT(2)-receptor activation tonically constricts the medullary circulation.
