Angiotensin II conditions the slow component of autoregulation of renal blood flow

1993 ◽  
Vol 264 (3) ◽  
pp. F515-F522 ◽  
Author(s):  
W. A. Cupples
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Slow Component ◽  
Renal Perfusion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Renal Autoregulation ◽  
Fitting In

Release of a suprarenal aortic clamp results in angiotensin-dependent, arterial pressure-mediated renal vasoconstriction. The experiments reported here were designed to show whether this represents operation of autoregulation and whether the slow component of autoregulation is affected by angiotensin II (ANG II). They were performed using halothane-anesthetized Sprague-Dawley rats. In the 1st experiment renal perfusion pressure (RPP) was reduced in steps from spontaneous level to 45 mmHg and then returned in steps to the spontaneous level. The autoregulatory plateau was left-shifted some 20-30 mmHg, with the lower limit of autoregulation reduced from approximately 85 mmHg on the downward leg to approximately 60 mmHg on the upward leg. This resetting was blocked by captopril. Two experiments examined low pressure autoregulation in more detail. After RPP was reduced, three pairs of steps between 65 and 75 mmHg were performed. Significant renal vasodilatation was observed after downward pressure steps in both experiments. Time constants (tau) of resistance adjustment were recovered from most steps by curve fitting. In both experiments tau down = 0.07 +/- 0.01 Hz was faster than tau up = 0.04 +/- 0.01 Hz. Blockade of ANG II by enalaprilat or by the AT1-receptor blocker losartan potassium significantly inhibited regulatory vasodilatation and vasoconstriction at low RPP. Also, tau down = 0.04 +/- 0.01 Hz collapsed to the value of tau up = 0.04 +/- 0.01 Hz. These results demonstrate a significant role for ANG II in renal autoregulation. They show that ANG II is necessary for autoregulation to reset to operate at reduced arterial pressure and to defend a lower blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II induces insulin resistance independent of changes in interstitial insulin

1999 ◽  
Vol 277 (5) ◽  
pp. E920-E926 ◽  
Author(s):  
Joyce M. Richey ◽  
Marilyn Ader ◽  
Donna Moore ◽  
Richard N. Bergman
Keyword(s):  
Insulin Resistance ◽  
Heart Rate ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glucose Uptake ◽  
Peripheral Resistance ◽  
Glucose Turnover ◽  
Ang Ii

We set out to examine whether angiotensin-driven hypertension can alter insulin action and whether these changes are reflected as changes in interstitial insulin (the signal to which insulin-sensitive cells respond to increase glucose uptake). To this end, we measured hemodynamic parameters, glucose turnover, and insulin dynamics in both plasma and interstitial fluid (lymph) during hyperinsulinemic euglycemic clamps in anesthetized dogs, with or without simultaneous infusions of angiotensin II (ANG II). Hyperinsulinemia per se failed to alter mean arterial pressure, heart rate, or femoral blood flow. ANG II infusion resulted in increased mean arterial pressure (68 ± 16 to 94 ± 14 mmHg, P < 0.001) with a compensatory decrease in heart rate (110 ± 7 vs. 86 ± 4 mmHg, P < 0.05). Peripheral resistance was significantly increased by ANG II from 0.434 to 0.507 mmHg ⋅ ml−1⋅ min ( P < 0.05). ANG II infusion increased femoral artery blood flow (176 ± 4 to 187 ± 5 ml/min, P < 0.05) and resulted in additional increases in both plasma and lymph insulin (93 ± 20 to 122 ± 13 μU/ml and 30 ± 4 to 45 ± 8 μU/ml, P < 0.05). However, glucose uptake was not significantly altered and actually had a tendency to be lower (5.9 ± 1.2 vs. 5.4 ± 0.7 mg ⋅ kg−1⋅ min−1, P > 0.10). Mimicking of the ANG II-induced hyperinsulinemia resulted in an additional increase in glucose uptake. These data imply that ANG II induces insulin resistance by an effect independent of a reduction in interstitial insulin.

The arterial depressor response to chronic low-dose angiotensin II infusion in female rats is estrogen dependent

2012 ◽  
Vol 302 (1) ◽  
pp. R159-R165 ◽  
Author(s):  
Amanda K. Sampson ◽  
Lucinda M. Hilliard ◽  
Karen M. Moritz ◽  
Merlin C. Thomas ◽  
Chris Tikellis ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Low Dose ◽  
Renin Angiotensin System ◽  
Female Rats ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Estrogen Replacement ◽  
Sprague Dawley ◽  
Arterial Pressure Regulation

The complex role of the renin-angiotensin-system (RAS) in arterial pressure regulation has been well documented. Recently, we demonstrated that chronic low-dose angiotensin II (ANG II) infusion decreases arterial pressure in female rats via an AT2R-mediated mechanism. Estrogen can differentially regulate components of the RAS and is known to influence arterial pressure regulation. We hypothesized that AT2R-mediated depressor effects evident in females were estrogen dependent and thus would be abolished by ovariectomy and restored by estrogen replacement. Female Sprague-Dawley rats underwent ovariectomy or sham surgery and were treated with 17β-estradiol or placebo. Mean arterial pressure (MAP) was measured via telemetry in response to a 2-wk infusion of ANG II (50 ng·kg−1·min−1 sc) or saline. MAP significantly decreased in females treated with ANG II (−10 ± 2 mmHg), a response that was abolished by ovariectomy (+4 ± 2 mmHg) and restored with estrogen replacement (−6 ± 2 mmHg). Cardiac and renal gene expression of components of the RAS was differentially regulated by estrogen, such that overall, estrogen shifted the balance of the RAS toward the vasodilatory axis. In conclusion, estrogen-dependent mechanisms offset the vasopressor actions of ANG II by enhancing RAS vasodilator pathways in females. This highlights the potential for these vasodilator pathways as therapeutic targets, particularly in women.

scholarly journals High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Tahereh Safari ◽  
Mehdi Nematbakhsh ◽  
Roger G. Evans ◽  
Kate M. Denton
Keyword(s):  
Angiotensin Ii ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Renal Perfusion ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Increased Risk ◽  
Angiotensin Type 2 Receptor

Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by45.7±1.9% in estradiol-treated rats but only by27.3±5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen.

Effect of furegrelate on renal plasma flow after angiotensin II infusion

1990 ◽  
Vol 68 (4) ◽  
pp. 500-504 ◽  
Author(s):  
Ravi D. Kaushal ◽  
Thomas W. Wilson
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Hydrolysis Product ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Acid Clearance ◽  
Thromboxane Synthetase

We had previously shown that selective thromboxane synthetase inhibition with furegrelate increases urinary excretion of 6-ketoPGF1α, the hydrolysis product of prostacyclin after stimulation of renal prostaglandin synthesis with furosemide. The present study assessed the functional significance of this "redirection" of prostaglandin formation using a more physiologic stimulus, angiotensin II. Sprague–Dawley rats (n = 27) were fitted with a transabdominal bladder cannula. Five days later they were given angiotensin II (10 mg∙kg−1∙min−1) by intravenous infusion. After 30 min, an infusion of furegrelate, 2 mg/kg, then 2 mg∙kg−1∙h−1, (n = 9); indomethacin, 2 mg/kg, then 2 mg∙kg−1∙h−1 (n = 9); or vehicle, 250 μL, then 0.018 mL/min (n = 9) was begun for 60 min. Clearance of [14C]para-aminohippuric acid was taken as a measure of renal plasma flow. Angiotensin II raised the mean arterial pressure in all groups. Administration of furegrelate or indomethacin did not change mean arterial pressure or heart rate. Angiotensin II reduced [14C]p-aminohippuric acid clearance by about 32% (1.42 ± 0.18 to 0.97 ± 0.07 mL∙min−1∙100 g−1, p < 0.05). Furegrelate attenuated this renal vasoconstriction (0.97 ± 0.07 to 1.38 ± 0.17 mL∙min−1∙100 g−1, p < 0.05), while indomethacin increased it by a further 32% (1.78 ± 0.12 to 1.20 ± 0.12 mL∙min−1∙100 g−1, p < 0.05). Vehicle alone had no effect. Furegrelate reduced serum thromboxane B2 by 90% (6.52 ± 0.030 to 0.7 ± 0.21 ng/100 μL, p < 0.05), while indomethacin reduced it by 73% (5.9 ± 0.99 to 1.4 ± 0.20 ng/100 μL, p < 0.05). We conclude that furegrelate attenuates the renal vasoconstriction of angiotensin II, presumably by enhancing the formation of vasodilator prostaglandins.Key words: angiotensin II, furegrelate, indomethacin, para-aminohippuric acid clearance.

Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney

1996 ◽  
Vol 270 (3) ◽  
pp. R630-R635 ◽  
Author(s):  
N. Parekh ◽  
L. Dobrowolski ◽  
A. P. Zou ◽  
M. Steinhausen
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Rat Kidney ◽  
Ang Ii ◽  
No Donor ◽  
Renal Vasoconstriction ◽  
Medullary Blood Flow ◽  
Series Of Experiments ◽  
Synthase Inhibitor

This study compared the vasoconstrictor action of angiotensin II (ANG II) and norepinephrine (NE) with different levels of nitric oxide (NO) in the kidney of anesthetized rats. In one series of experiments, the drugs were infused intravenously, and systemic NO content was reduced by a NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME). L-NAME significantly enhanced the renal blood flow (RBF) reduction produced by ANG II from 26 to 49%, but it had no significant effect on the change in RBF induced by NE. Medullary blood flow was not influenced by either ANG II or NE given alone or given after L-NAME. In the second series of experiments, all drugs were infused into the renal artery to avoid their systemic and, hence, extrarenal effects. In these experiments, renal content of NO was increased by the NO donor sodium nitroprusside (SNP), decreased by L-NAME, or restored by replacing endogenous NO by exogenous NO (L-NAME + SNP). Effects of both ANG II and NE on RBF were similarly and significantly attenuated by SNP (60% of control), enhanced by L-NAME (200% of control), and restored by L-NAME + SNP (90% of control, not significant). Our results indicate that NO attenuates the renal vasoconstriction due to ANG II or NE and that the antagonism between vasoconstrictors and NO is not due to a constrictor-induced production of NO because exogenous and endogenous NO were equally effective.

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.

Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow

2000 ◽  
Vol 279 (3) ◽  
pp. R1017-R1024 ◽  
Author(s):  
Charlotte Mehlin Sorensen ◽  
Paul Peter Leyssac ◽  
Ole Skott ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Lower Limit ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Renal Perfusion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Acute Changes

The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit of autoregulation from 85 ± 1 to 73 ± 2 mmHg ( P < 0.05) and regulated RBF to a lower level. Reduction of RPP to just above the lower limit of autoregulation (88 mmHg) induced regulation of RBF to a lower level within 10 min. Clamping [ANG II] per se reset the lower limit of autoregulation to 62 ± 5 mmHg. In this case, reduction in RPP to 50 mmHg did not induce a downregulation of RBF. We conclude that ANG II plays an important role in the resetting of the autoregulation limits. The ability to regulate RBF to a new level as a response to changes in RPP also depends on changes in [ANG II].

Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide

2007 ◽  
Vol 292 (1) ◽  
pp. H83-H92 ◽  
Author(s):  
Armin Just ◽  
Andrea J. M. Olson ◽  
Christina L. Whitten ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Vascular Remodeling ◽  
Oxygen Species ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Adrenergic Agonist ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats

NAD(P)H oxidases (NOX) and reactive oxygen species (ROS) are involved in vasoconstriction and vascular remodeling during hypertension produced by chronic angiotensin II (ANG II) infusion. These effects are thought to be mediated largely through superoxide anion (O2−) scavenging of nitric oxide (NO). Little is known about the role of ROS in acute vasoconstrictor responses to agonists. We investigated renal blood flow (RBF) reactivity to ANG II (4 ng), norepinephrine (NE, 20 ng), and α1-adrenergic agonist phenylephrine (PE, 200 ng) injected into the renal artery (ira) of anesthetized Sprague-Dawley rats. The NOX inhibitor apocynin (1–4 mg·kg−1·min−1 ira, 2 min) or the superoxide dismutase mimetic Tempol (1.5–5 mg·kg−1·min−1 ira, 2 min) rapidly increased resting RBF by 8 ± 1% ( P < 0.001) or 3 ± 1% ( P < 0.05), respectively. During NO synthase (NOS) inhibition ( Nω-nitro-l-arginine methyl ester, 25 mg/kg iv), the vasodilation tended to increase (apocynin 13 ± 4%, Tempol 10 ± 1%). During control conditions, both ANG II and NE reduced RBF by 24 ± 4%. Apocynin dose dependently reduced the constriction by up to 44% ( P < 0.05). Similarly, Tempol blocked the acute actions of ANG II and NE by up to 48–49% ( P < 0.05). In other animals, apocynin (4 mg·kg−1·min−1 ira) attenuated vasoconstriction to ANG II, NE, and PE by 46–62% ( P < 0.01). During NOS inhibition, apocynin reduced the reactivity to ANG II and NE by 60–72% ( P < 0.01), and Tempol reduced it by 58–66% ( P < 0.001). We conclude that NOX-derived ROS substantially contribute to basal RBF as well as to signaling of acute renal vasoconstrictor responses to ANG II, NE, and PE in normal rats. These effects are due to O2− rather than H2O2, occur rapidly, and are independent of scavenging of NO.

Role of protein kinase C in angiotensin II-induced renal vasoconstriction in genetically hypertensive rats

1996 ◽  
Vol 270 (6) ◽  
pp. F945-F952 ◽  
Author(s):  
X. Ruan ◽  
W. J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Renal Vasoconstriction ◽  
Kinase C ◽  
Pkc Activation ◽  
Genetically Hypertensive

The renal vasculature of young spontaneously hypertensive rats (SHR) responds to angiotensin II (ANG II) with exaggerated vasoconstriction, due in part to defective buffering by the adenosine 3',5'-cyclic monophosphate (cAMP) pathway. In vitro studies suggest greater activation of phospholipase C and protein kinase C (PKC) in cultured mesangial cells and vascular smooth muscle cells. The present studies evaluated the role of PKC activation in renal vascular responses to ANG II receptor activation and the relative contributions in SHR vs. Wistar-Kyoto control rats (WKY). Renal blood flow was measured in 8-wk-old anesthetized SHR and WKY pretreated with indomethacin. ANG II (2 ng) injection into the renal artery produced a transient 45-50% maximum reduction of renal blood flow in both rat strains. Intrarenal infusion of either staurosporine or chelerythrine into the renal artery effectively attenuated the vasoconstriction elicited by ANG II in a dose-dependent manner, with maximum inhibition of 60-70%. The PKC inhibitory effects were significant and independent of strain. Coadministration of the PKC inhibitors produced maximal inhibition similar to that observed with one agent, suggesting action via a common pathway. In other studies, the linkage of the PKC pathway to the AT1 receptor was evaluated using sub and maximal doses of losartan to antagonize 50-80% of ANG II-induced vasoconstriction. The same degree of inhibition was observed when a PKC inhibitor was coadministered with losartan. These findings support the views that the PKC system is a major intracellular signaling pathway coupled to the AT1 receptor in renal resistance vessels and that PKC activation is involved to similar degrees in the renal vasoconstriction elicited by ANG II in young WKY and SHR. Exaggerated vascular reactivity to vasoconstrictor agents in genetically hypertensive animals is probably due to a defect in cAMP generation in the presence of a normally operating PKC pathway.

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