Role of AT1 receptors in the renal papillary effects of acute and chronic nitric oxide inhibition

1998 ◽  
Vol 274 (3) ◽  
pp. R760-R766 ◽  
Author(s):  
M. Clara Ortíz ◽  
Lourdes A. Fortepiani ◽  
Francisco M. Ruiz-Marcos ◽  
Noemí M. Atucha ◽  
Joaquín García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Chronic Administration ◽  
Acute Administration ◽  
Synthesis Inhibitor ◽  
Renal Vasoconstriction ◽  
Oxide Inhibition ◽  
Stimulation Of

Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood flow (PBF) in the rat. In this study we have evaluated the role of AT1 angiotensin II receptors as modulators of the whole kidney and papillary vasoconstrictor effects induced by the acute or chronic inhibition of NO synthesis. Experiments have been performed in anesthetized, euvolemic Munich-Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal rats, acute administration of the NO synthesis inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) increased mean arterial pressure (MAP) and decreased RBF and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan did not modify the decreases in RBF or PBF secondary to l-NAME. In animals made hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and PBF were lower than in the controls. In these animals, acute or chronic administration of losartan decreased MAP and increased both RBF and PBF significantly. These results indicate that, under normal conditions, the decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not modulated by AT1-receptor stimulation. However, the arterial hypertension, renal vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive rats is partially due to the effects of angiotensin II, via stimulation of AT1-receptors.

scholarly journals Role of nitric oxide in long-term angiotensin II-induced renal vasoconstriction.

Hypertension ◽  
1993 ◽  
Vol 21 (6_pt_2) ◽  
pp. 949-955 ◽  
Author(s):  
R D Manning ◽  
L Hu ◽  
H L Mizelle ◽  
J P Granger
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Renal Vasoconstriction

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.

scholarly journals Role of Nitric Oxide in Regional Blood Flow in Angiotensin II-Induced Hypertensive Rats.

2001 ◽  
Vol 24 (4) ◽  
pp. 421-427 ◽  
Author(s):  
Akira NISHIYAMA ◽  
Yoshihide FUJISAWA ◽  
Toshiki FUKUI ◽  
Matlubur RAHMAN ◽  
Naoki KONDO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Regional Blood Flow ◽  
Hypertensive Rats

Regulation of endometrial blood flow in ovariectomized rats: assessment of the role of nitric oxide

1997 ◽  
Vol 273 (4) ◽  
pp. H2009-H2017
Author(s):  
Ren-Sheng Zhang ◽  
Paul H. Guth ◽  
Oscar U. Scremin ◽  
Rajan Singh ◽  
Shehla Pervin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Ovariectomized Rats ◽  
Acute Administration ◽  
Arterial Blood ◽  
Independent Mechanism ◽  
Estradiol 17Β ◽  
Endometrial Blood Flow

The purpose of this study was to evaluate the role of nitric oxide (NO) in the maintenance of basal endometrial blood flow of ovariectomized rats and in the increase of endometrial blood flow after administration of estradiol 17β (E2β). Endometrial blood flow was repeatedly measured with the H2 gas clearance technique in ovariectomized rats. N ω-nitro-l-arginine methyl ester (l-NAME) dose dependently reduced basal endometrial blood flow and increased mean arterial blood pressure and endometrial vascular resistance. E2β (1 μg/kg iv) increased endometrial blood flow and reduced endometrial vascular resistance, which peaked by 2 h after the injection. The vasoconstrictive activity of l-NAME (an inhibitor for NO synthesis) was compared with that of phenylephrine (PE, an α-receptor agonist acting through an NO-independent mechanism). Doses ofl-NAME (1 and 3 mg/kg iv) were matched with those of PE (3.2 and 6.4 mg ⋅ kg−1 ⋅ h−1iv), as they induced an approximately equivalent percent increase in basal endometrial vascular resistance. The percent increases of endometrial vascular resistance in E2β-treated animals by the two agents in matched doses were also of a similar magnitude. When animals were first treated with l-NAME or PE, E2β lost the ability to reduce endometrial vascular resistance. Enzyme activity and gene expression of NO synthase in the rat uterine tissue were also examined after E2β treatment, and no significant changes were observed. These data raise doubts about the role of NO in the regulation of endometrial blood flow after acute administration of E2β and suggest that other mechanisms may be involved.

Effects of Meclofenamate and Captopril on Renal and other Regional Vascular Beds after Mild Haemorrhage in Conscious Rabbits

1982 ◽  
Vol 62 (2) ◽  
pp. 169-176 ◽  
Author(s):  
R. A. Banks ◽  
L. J. Beilin ◽  
J. Soltys ◽  
L. Davidson
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Regional Blood Flow ◽  
Plasma Renin ◽  
Plasma Adrenaline ◽  
Renal Vasoconstriction ◽  
Vascular Beds ◽  
Conscious Rabbits

1. The role of prostaglandins and angiotensin II in blood flow regulation was studied in conscious rabbits subjected to mild haemorrhage. 2. Haemorrhage caused a 13% fall in arterial pressure and a 21% fall in cardiac output, responses which were unchanged by sodium meclofenamate, an inhibitor of prostaglandin synthesis, or captopril, an inhibitor of the angiotensin converting enzyme. 3. Haemorrhage doubled plasma adrenaline and noradrenaline levels. Plasma renin activity trebled after haemorrhage and was further elevated by captopril. 4. Renal blood flow was maintained after haemorrhage alone. Meclofenamate given immediately after haemorrhage caused a 31% fall in renal blood flow. Captopril given immediately after haemorrhage caused renal vasodilation, but when given after meclofenamate augmented renal vasoconstriction. 5. Splenic vasoconstriction was seen after haemorrhage and meclofenamate, and subsequently was augmented by captopril. 6. Results suggest that prostaglandins variably modulate regional blood flow in conscious rabbits subjected to mild haemorrhage. Enhanced sympathc—adrenal activity increases reno-vascular and splenic dependence on vasodilator prostaglandins, but not that of coronary, cerebral, hepatic or adrenal circulations. Renal and splenic vasoconstriction seen with meclofenamate are not due to circulating angiotensin 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.

Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats

1999 ◽  
Vol 277 (3) ◽  
pp. R725-R733 ◽  
Author(s):  
Axel C. Pflueger ◽  
Timothy S. Larson ◽  
Siegfried Hagl ◽  
Franklyn G. Knox
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Blood Flow ◽  
Experimental Diabetes ◽  
Capillary Blood ◽  
Experimental Diabetes Mellitus ◽  
Vasa Recta ◽  
Nondiabetic Control ◽  
Stimulation Of

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCC and QDV were significantly greater in STZ rats ( n = 16) compared with control rats ( n = 15). Infusion of N G-monomethyl-l-arginine (l-NMMA, 15 mg/kg bolus, 500 μg ⋅ min−1 ⋅ kg−1iv) decreased QCC (−41%), QAV (−38%), and QDV (−37%) in control rats ( n = 6) and to a significantly greater magnitude than in STZ rats ( n = 7), QCC (−14%), QAV (−20%), and QDV (−25%). Coinfusion ofl-arginine (l-Arg, 1 mg ⋅ kg−1 ⋅ min−1iv) with l-NMMA increased QCC to a significantly greater extent ( P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion ofl-Arg alone increased QCC (+50%), QAV (+16%), and QDV (+11%) in control rats ( n = 5) but had no effect in STZ rats ( n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.

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