Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs

2005 ◽  
Vol 288 (2) ◽  
pp. F412-F419 ◽  
Author(s):  
Dewan S. A. Majid ◽  
Akira Nishiyama ◽  
Keith E. Jackson ◽  
Alexander Castillo
Keyword(s):  
Nitric Oxide ◽  
Urinary Sodium Excretion ◽  
Ang Ii ◽  
Arterial Infusion ◽  
Anesthetized Dogs ◽  
Significant Attenuation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Renal Responses

To assess the role of superoxide (O2−) and nitric oxide (NO) interaction in mediating the renal actions of ANG II, we examined the renal responses to intra-arterial infusion of ANG II (0.5 ng·kg−1·min−1) before and during administration of a superoxide dismutase mimetic, tempol (0.5 mg·kg−1·min−1), in the presence or absence of NO synthase inhibitor, nitro-l-arginine (NLA; 50 μg·kg−1·min−1), in anesthetized dogs pretreated with enalaprilat (33 μg·kg−1·min−1). In one group of dogs ( n = 7), ANG II infusion before tempol infusion caused decreases of 24 ± 4% in renal blood flow (RBF), 55 ± 7% in urine flow (V), and 53 ± 8% in urinary sodium excretion (UNaV) with a slight decrease in glomerular filtration rate (GFR; −7.8 ± 3.4%). Tempol infusion alone did not cause significant alterations in RBF, GFR, V, or UNaV; however, ANG II in the presence of tempol caused a smaller degree of decreases in RBF (−12 ± 2%), in V (−16 ± 5%), and in UNaV (−27 ± 10%) with a slight increase in GFR (6.6 ± 2.8%) than the responses observed before tempol. In another group of NLA-treated dogs ( n = 6), tempol infusion also caused significant attenuation in the ANG II-induced responses on RBF (−13 ± 3% vs. −22 ± 7%), GFR (−19 ± 5% vs. −33 ± 3), V (−15 ± 12% vs. −28 ± 4%), and UNaV (−11 ± 14% vs. −32 ± 7%). These data demonstrate that renal responses to ANG II are partly mediated by O2− generation and its interaction with NO. The sodium-retaining effect of ANG II is greatly influenced by O2− generation, particularly in the condition of NO deficiency.

Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney

2004 ◽  
Vol 287 (1) ◽  
pp. R27-R32 ◽  
Author(s):  
Dewan S. A. Majid ◽  
Akira Nishiyama ◽  
Keith E. Jackson ◽  
Alexander Castillo
Keyword(s):  
Nitric Oxide ◽  
Protective Role ◽  
Potential Interaction ◽  
No Synthase ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor ◽  
Qualitative Responses ◽  
Oxide Synthase ◽  
Renal Responses

To evaluate the role of a potential interaction between superoxide anion (O2−) and nitric oxide (NO) in regulating kidney function, we examined the renal responses to intra-arterial infusion of a superoxide dismutase mimetic, tempol (0.5 mg·kg−1·min−1), in anesthetized dogs treated with or without NO synthase inhibitor, Nω-nitro-l-arginine (NLA; 50 μg·kg−1·min−1). In one group of dogs ( n = 10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 ± 0.4 to 5.0 ± 0.4 ml·min−1·g−1), glomerular filtration rate (GFR; 0.79 ± 0.04 to 0.77 ± 0.04 ml·min−1·g−1), urine flow (V; 13.6 ± 2.1 to 13.9 ± 2.5 μl·min−1·g−1), or sodium excretion (UNaV; 2.4 ± 0.3 to 2.2 ± 0.3 μmol·min−1·g−1). Interestingly, when tempol was infused in another group of dogs ( n = 12) pretreated with NLA, it caused increases in V (4.4 ± 0.4 to 9.7 ± 1.4 μl·min−1·g−1) and in UNaV (0.7 ± 0.1 to 1.3 ± 0.2 μmol·min−1·g−1) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 ± 5 vs. 26 ± 4%) and antinatriuretic (67 ± 4 vs. 45 ± 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 ± 2.7 to 22.8 ± 3.6 pg·min−1·g−1; n = 7), which returned to the control levels (11.6 ± 3.4 pg·min−1·g−1) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O2− levels and support the hypothesis that NO plays a protective role against the actions of O2− in the kidney.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

scholarly journals Vasoactivity of adenosine in the trout (Oncorhynchus mykiss) coronary system: involvement of nitric oxide and interaction with noradrenaline

1998 ◽  
Vol 201 (22) ◽  
pp. 3075-3083 ◽  
Author(s):  
T Mustafa ◽  
C Agnisola
Keyword(s):  
Nitric Oxide ◽  
Constant Pressure ◽  
Constant Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Heart Preparation ◽  
Synthase Inhibitor ◽  
Coronary Endothelium ◽  
Oxide Synthase ◽  
Working Heart

A vasoconstrictory response to adenosine has been reported in coronary rings from fish. Since the reactivity of the large coronary arteries and the microcirculation may differ, the present study was undertaken to determine the role of adenosine in the intact coronary system of trout under constant pressure or flow using an isolated and non-working heart preparation. The involvement of nitric oxide (NO) and the interaction with noradrenaline were also studied. At 10(-9) to 10(-8 )mol l-1, adenosine caused a vasoconstrictory response, whereas between 10(-7) and 10(-5 )mol l-1 the response was predominantly vasodilative. Theophylline abolished both these responses to adenosine. The vasodilation induced by adenosine (at 10(-5 )mol l-1) was significantly reduced when the preparation was perfused under constant-flow than rather under constant-pressure conditions. The nitric oxide synthase inhibitor N-nitro-l-arginine (l-NA, 10(-4 )mol l-1) partially reduced the vasodilation induced by adenosine (at 10(-5 )mol l-1) under constant-pressure but not under constant-flow conditions. Perfusion of the intact coronary system with l-arginine or with adenosine significantly increased the rate of nitrite (NO2-) release, while perfusion with l-NA or theophylline reduced NO2- release. Chemical denudation of the coronary endothelium by CHAPS resulted in the loss of both the l-arginine- and adenosine-mediated vasodilation and the l-arginine-induced increase in the rate of NO2- release. Adenosine (10(-5 )mol l-1) offset and overrode the vasoconstriction induced by 10(-7 )mol l-1 noradrenaline. l-NA inhibited only the adenosine-induced vasodilation but not the ability to offset noradrenaline vasoconstriction, excluding the involvement of NO in the interaction between adenosine and noradrenaline.

Mechanisms of angiotensin II natriuresis and antinatriuresis

1985 ◽  
Vol 249 (2) ◽  
pp. F299-F307 ◽  
Author(s):  
M. E. Olsen ◽  
J. E. Hall ◽  
J. P. Montani ◽  
A. C. Guyton ◽  
H. G. Langford ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sodium Excretion ◽  
Distal Tubule ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Sodium Load ◽  
Proximal Tubular ◽  
Anesthetized Dogs

The aim of this study was to determine the role of changes in renal arterial pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (ANG II). In seven anesthetized dogs, endogenous ANG II formation was blocked with captopril, and ANG II was infused intravenously at rates of 5-1,215 ng X kg-1 X min-1 while RAP was either servo-controlled at the preinfusion level or permitted to increase. When RAP was servo-controlled, ANG II infusion at all rates from 5-1,215 ng X kg-1 X min-1 decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) while increasing fractional reabsorption of lithium (FRLi) (an index of proximal tubular fractional sodium reabsorption) and causing no change in calculated distal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng X kg-1. min-1 also decreased UNaV and FENa while increasing FRLi and causing no change in FRDNa. However, at 135 ng X kg-1 X min-1 and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion compared with when RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause antinatriuresis when RAP is prevented from increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of prostaglandins and endothelium-derived relaxing factor on the renal response to acetylcholine

1991 ◽  
Vol 260 (1) ◽  
pp. F145-F149 ◽  
Author(s):  
M. G. Salom ◽  
V. Lahera ◽  
J. C. Romero
Keyword(s):  
Urine Volume ◽  
Urinary Sodium Excretion ◽  
Diuretic Effect ◽  
Simultaneous Administration ◽  
Relaxing Factor ◽  
Blocking Effects ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Renal Responses

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.

Effects of nitric oxide synthase inhibition on cutaneous vasodilation during body heating in humans

1998 ◽  
Vol 85 (3) ◽  
pp. 830-834 ◽  
Author(s):  
Shubha Shastry ◽  
Niki M. Dietz ◽  
John R. Halliwill ◽  
Ann S. Reed ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Potential Role ◽  
Contralateral Side ◽  
Laser Doppler ◽  
Cutaneous Vasodilation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Blood

We sought to examine further the potential role of nitric oxide (NO) in the neurally mediated cutaneous vasodilation in nonacral skin during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured by using laser-Doppler flowmeters placed on both forearms. The NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA) was given selectively to one forearm via a brachial artery catheter after marked cutaneous vasodilation had been established. During body heating, oral temperature increased by 1.1 ± 0.1°C while heart rate increased by 30 ± 6 beats/min. Mean arterial pressure stayed constant at 84 ± 2 mmHg. In the experimental forearm, cutaneous vascular conductance (CVC; laser-Doppler) decreased to 86 ± 5% of the peak response to heating ( P < 0.05 vs. pre-l-NMMA values) afterl-NMMA infusion. In some subjects, l-NMMA caused CVC to fall by ∼30%; in others, it had little impact on the cutaneous circulation. CVC in the control arm showed a similar increase with heating, then stayed constant whilel-NMMA was given to the contralateral side. These results demonstrate that NO contributes modestly, but not consistently, to cutaneous vasodilation during body heating in humans. They also indicate that NO is not the only factor responsible for the dilation.

scholarly journals Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation

2012 ◽  
Vol 302 (2) ◽  
pp. E201-E208 ◽  
Author(s):  
Jeong-a Kim ◽  
Hyun-Ju Jang ◽  
Luis A. Martinez-Lemus ◽  
James R. Sowers
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vascular Endothelium ◽  
Endothelial Nitric Oxide Synthase ◽  
Point Mutations ◽  
Ang Ii ◽  
Cardiovascular Tissues ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Elevated tissue levels of angiotensin II (ANG II) are associated with impairment of insulin actions in metabolic and cardiovascular tissues. ANG II-stimulated activation of mammalian target of rapamycin (mTOR)/p70 S6 kinase (p70S6K) in cardiovascular tissues is implicated in cardiac hypertrophy and vascular remodeling. However, the role of ANG II-stimulated mTOR/p70S6K in vascular endothelium is poorly understood. In the present study, we observed that ANG II stimulated p70S6K in bovine aortic endothelial cells. ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser636/639 and inhibited the insulin-stimulated phosphorylation of endothelial nitric oxide synthase (eNOS). An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser636/639) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Moreover, point mutations of IRS-1 at Ser636/639 to Ala prevented the ANG II-mediated inhibition of insulin signaling. From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin-stimulated vasodilation through phosphorylation of IRS-1 at Ser636/639. This ANG II-mediated impairment of vascular actions of insulin may help explain the role of ANG II as a link between insulin resistance and hypertension.

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