scholarly journals Mice lacking the ADP ribosyl cyclase CD38 exhibit attenuated renal vasoconstriction to angiotensin II, endothelin-1, and norepinephrine

2009 ◽  
Vol 297 (1) ◽  
pp. F169-F176 ◽  
Author(s):  
Tiffany L. Thai ◽  
William J. Arendshorst
Keyword(s):  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Pressor Response ◽  
Family Members ◽  
Cell Types ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Endothelin 1 ◽  
Adp Ribosyl Cyclase ◽  
Renal Vascular

ADP ribosyl (ADPR) cyclases comprise a family of ectoenzymes recently shown to influence cytosolic Ca2+concentration in a variety of cell types. At least two ADPR cyclase family members have been identified in mammals: CD38 and CD157. We recently found reduced renal vascular reactivity to angiotensin II (ANG II), endothelin-1 (ET-1), and norepinephrine (NE) in the presence of the broad ADPR cyclase inhibitor nicotinamide. We hypothesized that CD38 mediates effects attributed to ADPR cyclase. We found expression of ADPR cyclases CD38 and CD157 mRNA in spleen, thymus, skin, and preglomerular arterioles of wild-type (WT) animals. Mice lacking CD38 showed decreased CD157 expression in most tissues tested. No difference in systolic or mean arterial pressure was observed between strains in either conscious or anesthetized states, whereas heart rate was reduced 10–20% in CD38−/− animals ( P < 0.05). During anesthesia, CD38−/− mice had reduced basal renal blood flow (RBF) and urine excretion ( P < 0.05). RBF responses to intravenous injection of ANG II, ET-1, and NE were attenuated ∼50% in CD38−/− vs. WT mice ( P < 0.01 for all). The systemic pressor response to ANG II was decreased in the absence of CD38 ( P < 0.01), whereas that to NE was normal ( P > 0.05); ET-1 was administered at a nonpressor dose. Nicotinamide effectively inhibited ANG II-induced renal vasoconstriction in WT mice ( P < 0.001), but had no effect on renal responses to ANG II in CD38−/− mice ( P > 0.5). Overall, our observations indicate the presence of two ADPR cyclase family members in renal preglomerular resistance arterioles and the importance of CD38 participation in acute vascular responses to all three vasoconstrictors in the renal microcirculation.

Cyclosporine augments renal but not systemic vascular reactivity

1990 ◽  
Vol 258 (1) ◽  
pp. F211-F217
Author(s):  
M. D. Garr ◽  
M. S. Paller
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Arginine Vasopressin ◽  
Vascular Reactivity ◽  
Pressor Response ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Vascular Responsiveness ◽  
Renal Vascular

Renal vasoconstriction and hypertension are major side effects of cyclosporine. We tested the acute effects of cyclosporine on renal and systemic vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin. Renal vascular reactivity was tested in anesthetized Sprague-Dawley rats with denervated kidneys. Renal blood flow was measured with an electromagnetic flow probe in response to graded intra-arterial infusions of vasoconstrictors before and after intravenous administration of cyclosporine. Cyclosporine augmented the decrease in renal blood flow and the increase in renal vascular resistance produced by intrarenal norepinephrine, angiotensin II, and arginine vasopressin. In these studies, systemic blood pressure did not change and cyclosporine caused no direct change in basal renal blood flow. In contrast, in conscious animals, cyclosporine did not increase the pressor response to intravenous norepinephrine or to angiotensin II. Rather, cyclosporine caused enhanced baroreflex slowing of heart rate and a decrease in the pressor response to both norepinephrine and angiotensin II. Even when the baroreceptor reflex was blocked by pentolinium, the pressor response to norepinephrine in cyclosporine-treated animals was diminished compared with vehicle-treated animals. Therefore, although cyclosporine augmented renal vasoconstriction in response to norepinephrine, angiotensin II, and arginine vasopressin, it did not acutely increase the systemic vascular response to these agents. Enhanced renal vascular responsiveness is an additional mechanism for cyclosporine-mediated renal vasoconstriction. Lack of enhanced peripheral vascular responsiveness suggests that hypertension is not likely to be due to direct effects on the systemic vasculature and is more likely to be a consequence of renal functional impairment.

Angiotensin-induced defects in renal oxygenation: role of oxidative stress

2005 ◽  
Vol 288 (1) ◽  
pp. H22-H28 ◽  
Author(s):  
William J. Welch ◽  
Jonathan Blau ◽  
Hui Xie ◽  
Tina Chabrashvili ◽  
Christopher S. Wilcox
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Glass Electrode ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Mrna And Protein Expression ◽  
Renal Vascular ◽  
Induced Defects ◽  
Renal Oxygen

We tested the hypothesis that superoxide anion (O2−·) generated in the kidney by prolonged angiotensin II (ANG II) reduces renal cortical Po2 and the use of O2 for tubular sodium transport (TNa:QO2). Groups ( n = 8–11) of rats received angiotensin II (ANG II, 200 ng·kg−1·min−1 sc) or vehicle for 2 wk with concurrent infusions of a permeant nitroxide SOD mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, 200 nmol·kg−1·min−1) or vehicle. Rats were studied under anesthesia with measurements of renal oxygen usage and Po2 in the cortex and tubules with a glass electrode. Compared with vehicle, ANG II increased mean arterial pressure (107 ± 4 vs. 146 ± 6 mmHg; P < 0.001), renal vascular resistance (42 ± 3 vs. 65 ± 7 mmHg·ml−1·min−1·100 g−1; P < 0.001), renal cortical NADPH oxidase activity (2.3 ± 0.2 vs. 3.6 ± 0.4 nmol O2−··min−1·mg−1 protein; P < 0.05), mRNA and protein expression for p22 phox (2.1- and 1.8-fold respectively; P < 0.05) and reduced the mRNA for extracellular (EC)-SOD (−1.8 fold; P < 0.05). ANG II reduced the Po2 in the proximal tubule (39 ± 1 vs. 34 ± 2 mmHg; P < 0.05) and throughout the cortex and reduced the TNa:QO2 (17 ± 1 vs. 9 ± 2 μmol/μmol; P < 0.001). Tempol blunted or prevented all these effects of ANG II. The effects of prolonged ANG II to cause hypertension, renal vasoconstriction, renal cortical hypoxia, and reduced efficiency of O2 usage for Na+ transport, activation of NADPH oxidase, increased expression of p22 phox, and reduced expression of EC-SOD can be ascribed to O2−· generation because they are prevented by an SOD mimetic.

Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine

2004 ◽  
Vol 286 (2) ◽  
pp. F323-F330 ◽  
Author(s):  
Joen Steendahl ◽  
Niels-Henrik Holstein-Rathlou ◽  
Charlotte Mehlin Sorensen ◽  
Max Salomonsson
Keyword(s):  
Angiotensin Ii ◽  
Niflumic Acid ◽  
Channel Blockers ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Renal Vasoconstriction ◽  
Electromagnetic Flowmetry ◽  
Control Response ◽  
Renal Vascular

The aim of the present study was to investigate the role of Ca2+-activated Cl- channels in the renal vasoconstriction elicited by angiotensin II (ANG II) and norepinephrine (NE). Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry. Ratiometric photometry of fura 2 fluorescence was used to estimate intracellular free Ca2+ concentration ([Ca2+]i) in isolated preglomerular vessels from rat kidneys. Renal arterial injection of ANG II (2-4 ng) and NE (20-40 ng) produced a transient decrease in RBF. Administration of ANG II (10-7 M) and NE (5 × 10-6 M) to the isolated preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of DIDS (0.6 and 1.25 μmol/min) attenuated the ANG II-induced vasoconstriction to ∼35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 μmol/min) and 2-[(2-cyclopentenyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1 H-inden-5-yl)oxy]acetic acid (IAA-94; 0.045 and 0.09 μmol/min) did not affect the vasoconstrictive responses of these compounds. Pretreatment with niflumic acid (50 μM) or IAA-94 (30 μM) for 2 min decreased baseline [Ca2+]i but did not change the magnitude of the [Ca2+]i response to ANG II and NE in the isolated vessels. The present results do not support the hypothesis that Ca2+-activated Cl- channels play a crucial role in the hemodynamic effects of ANG II and NE in rat renal vasculature.

Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

2007 ◽  
Vol 293 (4) ◽  
pp. H2537-H2542 ◽  
Author(s):  
David W. Stepp ◽  
Erika I. Boesen ◽  
Jennifer C. Sullivan ◽  
James D. Mintz ◽  
Clark D. Hair ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zucker Rats ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Insulin Resistant

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.

Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE

2006 ◽  
Vol 291 (4) ◽  
pp. R977-R986 ◽  
Author(s):  
E. Joly ◽  
R. Seqqat ◽  
B. Flamion ◽  
N. Caron ◽  
A. Michel ◽  
...  
Keyword(s):  
Protein Expression ◽  
Vascular Reactivity ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Cyclooxygenase 1 ◽  
Resistance Vessels ◽  
Male Wistar Rats ◽  
Renal Vascular ◽  
Cytochrome P 450

This study examined the role of intrarenal ANG II in the renal vascular reactivity changes occurring in the remaining kidney undergoing adaptation following contralateral nephrectomy. Renal blood flow responses to intrarenal injections of ANG II (0.25 to 5 ng) were measured in anesthetized euvolemic male Wistar rats 1, 4, 12, and 24 wk after uninephrectomy (UNX) or sham procedure (SHAM). At week 4, renal vasoconstriction induced by 2 ng ANG II was greater in UNX (69 ± 5%) than in SHAM rats (50 ± 3%; P < 0.01). This response was inhibited, by 50 and 66%, and by 20 and 25%, in SHAM and UNX rats, after combined injections of ANG II and losartan, or PD-123319 ( P < 0.05), respectively. Characteristics of ANG II receptor binding in isolated preglomerular resistance vessels were similar in the two groups. After prostanoid inhibition with indomethacin, renal vasoconstriction was enhanced by 42 ± 8% ( P < 0.05), only in SHAM rats, whereas after 20-HETE inhibition with HET0016, it was reduced by 53 ± 16% ( P < 0.05), only in UNX rats. These differences vanished after concomitant prostanoid and 20-HETE inhibition in the two groups. After UNX, renal cortical protein expression of cytochrome P-450 2c23 isoform (CYP2c23) and cyclooxygenase-1 (COX-1) was unaltered, but it was decreased for CYP4a and increased for COX-2. In conclusion, renal vascular reactivity to ANG II was significantly increased in the postuninephrectomy adapted kidney, independently of protein expression, but presumably involving interactions between 20-HETE and COX in the renal microvasculature and changes in the paracrine activity of ANG II and 20-HETE.

scholarly journals Angiotensin II and the Renal Hemodynamic Response to an Isolated Increased Renal Venous Pressure in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaohua Huang ◽  
Shereen M. Hamza ◽  
Wenqing Zhuang ◽  
William A. Cupples ◽  
Branko Braam
Keyword(s):  
Angiotensin Ii ◽  
Ace Inhibitor ◽  
Venous Pressure ◽  
Ace Inhibition ◽  
Hemodynamic Response ◽  
Systemic Effect ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Renal Hemodynamic ◽  
Renal Vascular

Elevated central venous pressure increases renal venous pressure (RVP) which can affect kidney function. We previously demonstrated that increased RVP reduces renal blood flow (RBF), glomerular filtration rate (GFR), and renal vascular conductance (RVC). We now investigate whether the RAS and RBF autoregulation are involved in the renal hemodynamic response to increased RVP. Angiotensin II (ANG II) levels were clamped by infusion of ANG II after administration of an angiotensin-converting enzyme (ACE) inhibitor in male Lewis rats. This did not prevent the decrease in ipsilateral RBF (−1.9±0.4ml/min, p&lt;0.05) and GFR (−0.77±0.18ml/min, p&lt;0.05) upon increased RVP; however, it prevented the reduction in RVC entirely. Systemically, the RVP-induced decline in mean arterial pressure (MAP) was more pronounced in ANG II clamped animals vs. controls (−22.4±4.1 vs. −9.9±2.3mmHg, p&lt;0.05), whereas the decrease in heart rate (HR) was less (−5±6bpm vs. −23±4bpm, p&lt;0.05). In animals given vasopressin to maintain a comparable MAP after ACE inhibition (ACEi), increased RVP did not impact MAP and HR. RVC also did not change (0.018±0.008ml/minˑmmHg), and the reduction of GFR was no longer significant (−0.54±0.15ml/min). Furthermore, RBF autoregulation remained intact and was reset to a lower level when RVP was increased. In conclusion, RVP-induced renal vasoconstriction is attenuated when ANG II is clamped or inhibited. The systemic effect of increased RVP, a decrease in HR related to a mild decrease in blood pressure, is attenuated also during ANG II clamp. Last, RBF autoregulation remains intact when RVP is elevated and is reduced to lower levels of RBF. This suggests that in venous congestion, the intact RBF autoregulation could be partially responsible for the vasoconstriction.

scholarly journals Role of protein kinase C in renal vasoconstriction caused by angiotensin II

1990 ◽  
Vol 259 (3) ◽  
pp. C421-C426 ◽  
Author(s):  
H. Scholz ◽  
A. Kurtz
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Rat Kidney ◽  
Channel Blockers ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Protein Kinase C Inhibitors ◽  
Kinase C ◽  
Renal Vascular

In this study we have examined the subcellar pathways along which angiotensin II (ANG II) causes renal vasoconstriction. Using the isolated perfused rat kidney model, we found that renal vasoconstriction produced by ANG II (100 pM) was not altered by the calmodulin antagonists calmidazolium (1 microM) and N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7, 10 microM) but was blunted by staurosporine (100 nM) and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7, 50 microM), two structurally distinct putative protein kinase C inhibitors. The phorbol ester 4 alpha-phorbol 12,13-didecanoate (1-100 nM) did not alter renal vascular resistance, whereas phorbol 12-myristate 13-acetate (PMA, 1-100 nM) caused potent and dose-dependent vasoconstriction that was prevented by staurosporine (100 nM) and H-7 (50 microM). The vasoconstrictory effects of ANG II and PMA were attenuated by the calcium channel blockers verapamil (5 microM) and nifedipine (5 microM) and were reversibly inhibited when cobaltous chloride (2 mM) was added to the perfusate. Taken together, our findings support the concept that the renal vasoconstrictory effect of ANG II is essentially mediated by protein kinase C activation, which either requires or enhances the entrance of extracellular calcium.

Inhibition by Bradykinin of the Vascular Effects of Pressor Hormones in the Canine Kidney: Relationship to Prostaglandins

1980 ◽  
Vol 59 (s6) ◽  
pp. 145s-148s ◽  
Author(s):  
H. Sušić ◽  
A. Nasjletti ◽  
K. U. Malik
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Vascular Reactivity ◽  
Sodium Pentobarbital ◽  
Vascular Effects ◽  
Arterial Infusion ◽  
Renal Vasoconstriction ◽  
Renal Vascular ◽  
Canine Kidney

1. Renal arterial injection of bolus doses of angiotensin II or noradrenaline, (0.06, 0.12 and 0.25 μg) caused renal vasoconstriction and decreased blood flow to the kidney in a dose-related manner in dogs anaesthetized by sodium pentobarbital. 2. The effect of angiotensin II and noradrenaline in lowering renal blood flow was reduced during renal arterial infusion of either bradykinin (10 ng min−1 kg−1) or prostaglandin E2 (4 ng min−1 kg−1). 3. Pretreatment of the dogs with an inhibitor of prostaglandin synthesis, sodium meclofenamate (5 mg/kg), blunted the inhibitory action of bradykinin, but not that of prostaglandin E2, on renal vascular reactivity to angiotensin II and noradrenaline. 4. These results indicate that bradykinin reduces the renal vasoconstriction induced by angiotensin II and noradrenaline in the dog by a mechanism dependent upon synthesis of prostaglandins.

Vascular reactivity to angiotensin II in the normotensive and hypertensive pregnant ewe

1980 ◽  
Vol 238 (2) ◽  
pp. H209-H213
Author(s):  
S. M. Lieb ◽  
T. Cabalum ◽  
M. Zugaib ◽  
R. Erkkola ◽  
K. Tabsh ◽  
...  
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Pressor Response ◽  
Renal Hypertension ◽  
Circulatory Response ◽  
Pregnant Sheep ◽  
Experimental Renal Hypertension ◽  
Pregnant Ewe ◽  
Renal Vascular

The circulatory responses to progressively increasing doses of angiotensin II were studied in the same group of chronically instrumented unanesthetized pregnant sheep during three consecutive periods: a) normotensive with intact kidneys; b) normotensive with unilateral nephrectomy; and c) one-kidney hypertension. The results show that 1) the pressor response to a given dose of angiotensin was significantly greater in the normotensive than in the hypertensive condition; 2) uterine blood flow decreased markedly with the development of hypertension; 3) uterine circulatory response to angiotensin depended on the dosage; the response was less the the hypertensive than in the normotensive condition; 4) renal blood flow decreased and renal vascular resistance increased during angiotensin infusion, but the response was less in the hypertensive than in the normotensive condition; the response of the renal circulation decreased with increasing doses of angiotensin. These observations suggest a generalized vascular refractoriness to exogenous angiotensin II in the pregnant ewe with experimental renal hypertension.

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