Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats

Tost, H; Hably, Csilla; Lengyel, Miléna; Gógl, A; Lendvai, A.; Bartha, J

doi:10.1017/s0958067000020856

Cited by 5 publications

(7 citation statements)

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“…These increases in SBP and PP may be due in part to the removal of relaxation normally caused by NO. There have been several reports demonstrating decreased renal blood flow, increased renal vascular resistance and elevated SBP after treatment with non‐selective NOS inhibitors in rats . Our results are according to these statements, since, in the presence of L‐NAME, the administration of a NOS substrate, l ‐arginine, was able to return to baseline values of haemodynamic variables (see Table ).…”

Section: Discussionsupporting

confidence: 87%

Pharmacological evidence that 5‐HT_1D activation induces renal vasodilation by NO pathway in rats

García-Pedraza

García

Martín

et al. 2015

Clin Exp Pharma Physio

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5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5-HT₂ activation). Nevertheless, 5-HT is notable for its dual cardiovascular effects, producing both vasodilator and vasoconstrictor actions. This study aimed to investigate whether, behind the predominant serotonergic vasoconstrictor action, THE 5-HT system may exert renal vasodilator actions, and, if so, characterize the 5-HT receptors and possible indirect pathways. Renal perfusion pressure (PP), systemic blood pressure (SBP) and heart rate (HR) measurement in in situ autoperfused rat kidney was determined in phenylephrine infused rats. Intra arterial (i.a.) bolus administration of 5-HT (0.00000125-0.1 μg/kg) decreased renal PP in the presence of a phenylephrine continuous infusion (phenylephrine-infusion group), without modifying SBP or HR. These vasodilator responses were potentiated by 5-HT₂ antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5-HT₁ /₇ antagonist (methiothepin, 100 μg/kg i.v.) or 5-HT1D antagonist (LY310762, 1 mg/kg i.v.). The i.a. administration (0.00000125 to 0.1 μg/kg) of 5-CT or L-694,247 (5-HT1D agonist) mimicked 5-HT vasodilator effect, while other agonists (1-PBG, α-methyl-5-HT, AS-19 (5-HT₇), 8-OH-DPAT (5-HT1A) or CGS-12066B (5-HT1B)) did not alter baseline haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5-HT1D, 1 mg/kg) or L-NAME (nitric oxide, 10 mg/kg), but not by i.v. bolus of indomethacin (cyclooxygenase, 2 mg/kg) or glibenclamide (ATP-dependent K(+) channel, 20 mg/kg). These outcomes suggest that 5-HT1D activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine-infusion rats mediated by the NO pathway.

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Section: Discussionsupporting

confidence: 87%

Pharmacological evidence that 5‐HT_1D activation induces renal vasodilation by NO pathway in rats

García-Pedraza

García

Martín

et al. 2015

Clin Exp Pharma Physio

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“…The most sensitive index affected during systemic inhibition of NO was the decrease of sodium and water excretion and the elevation of intrarenal vascular resistance. 27 The infusion of small doses of angiotensin II in experimental animal models also produced an increase in intrarenal vascular resistance and a fall in water and sodium excretion before peripheral systemic resistance and blood pressure started to rise. [28][29][30] By and large, these observations are consistent with the idea that the effects of NO on the renal microvasculature and tubular sodium handling continuously counterbalance those of angiotensin II.…”

Section: Discussionmentioning

confidence: 99%

Urinary nitric oxide metabolites and individual blood pressure progression to overt hypertension

Baumann

Schmaderer

Kuznetsova

et al. 2011

European Journal of Cardiovascular Prevention & Rehabilitat

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Baseline blood pressure (BP) is the strongest known determinant of progression to hypertension, but for an individualized prediction of the incidence of hypertension, the identification of additional biomarkers is crucial. In animal models of hypertension, renal nitric oxide (NO) handling modifies the systemic BP responses prior to the development of hypertension. This study aimed to evaluate whether urinary NO metabolites (NOx) predict the progression of hypertension in normotensive subjects. Among 62 participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes, we assessed progression to hypertension over 4.6 years. In a case-control design, 49 normotensive subjects including 10 subjects with high-normal blood pressure were enrolled of whom 25 remained normotensive (controls), whereas 24 'progressed' to hypertension (progressors). Thirteen hypertensive patients served as negative controls. Urinary NOx concentration, renal function and the urinary excretion of electrolytes were assessed at baseline and follow-up. At baseline, progressors showed higher BP values than controls and urinary NOx concentration was significantly lower in progressors as compared to the normotensive controls (p < 0.01). In all initially normotensive subjects baseline urinary NOx concentration was associated with follow-up BP (r = -0.55, p < 0.001) and the relative increase of BP over time (r = -0.47, p < 0.001). In progressors baseline urinary NOx was associated with follow-up BP (r = -0.52, p < 0.009) and the relative increase of BP over time (r = -0.44, p = 0.033). Baseline urinary NOx and BP were independent predictors for the relative BP increase. A urinary NOx threshold of <130.5 mg/L predicted 75% of all progressors. In context with high-normal baseline BP, 87.5% of all progressors were identified. These findings indicate that urinary NO metabolites are associated with BP development in normotensive subjects. Moreover, urinary NOx predicts the progression to hypertension independent of baseline BP suggesting urinary NOx as a biomarker for individual new-onset hypertension.

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“…However, L-NMMA-related inhibition of basal NO production has been associated with contrasting renal and systemic effects in both normal animals and humans. Indeed, the administration of L-NMMA impaired renal hemodynamics and function, though systemic hemodynamics were improved (22,26,27). On the other hand, L-NMMA-related NO inhibition has been associated with a direct tubular antinatriuretic effect as well as an antidiuretic effect (26,27), which may be attenuated by a progressive increase in blood pressure (28).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the administration of L-NMMA impaired renal hemodynamics and function, though systemic hemodynamics were improved (22,26,27). On the other hand, L-NMMA-related NO inhibition has been associated with a direct tubular antinatriuretic effect as well as an antidiuretic effect (26,27), which may be attenuated by a progressive increase in blood pressure (28). The parallel alterations in renal tubular sodium excretion and nitric oxide levels in the absence of changes in GFR and ERPF in the first 4-hr period indicates that a direct effect of MBmediated NO inhibition on renal sodium handling could also be suggested in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

et al. 2005

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Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.

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Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats

Cited by 5 publications

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Pharmacological evidence that 5‐HT_1D activation induces renal vasodilation by NO pathway in rats

Pharmacological evidence that 5‐HT_1D activation induces renal vasodilation by NO pathway in rats

Urinary nitric oxide metabolites and individual blood pressure progression to overt hypertension

Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

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Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats

Cited by 5 publications

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Pharmacological evidence that 5‐HT1D activation induces renal vasodilation by NO pathway in rats

Pharmacological evidence that 5‐HT1D activation induces renal vasodilation by NO pathway in rats

Urinary nitric oxide metabolites and individual blood pressure progression to overt hypertension

Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

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Pharmacological evidence that 5‐HT_1D activation induces renal vasodilation by NO pathway in rats

Pharmacological evidence that 5‐HT_1D activation induces renal vasodilation by NO pathway in rats