Influence of basal nitric oxide secretion on cardiac function in man.

Abstract

1 Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. placebo. 3 A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-' h-1) and systemic vascular resistance index (at 0.5 mg kg-' h-1) were seen.4 L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5 The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6 In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters.

Hemodynamic, renal, and endocrine effects of acute inhibition of nitric oxide synthase in compensated cirrhosis

“…These investigations [45][46][47][48][49][50][51][52] agree on indicating that inhibition of NO synthesis results in hemodynamic changes qualitatively similar to those observed in the current study, i.e., increments of MAP and systemic vascular resistance and reductions in cardiac output, heart rate, and stroke volume. However, in healthy subjects inhibition of NOS had quite different renal effects from those observed in cirrhotic patients in our study because it induced reductions of variable degrees in RBF, GFR, and sodium excretion, which occurred despite an increase in MAP, 49,[52][53][54][55][56][57] indicating that NO acts as a regulator of renal hemodynamics and sodium excretion in healthy humans.…”

“…Several studies have been published investigating the effects of NOS inhibition on systemic hemodynamics [45][46][47][48][49][50][51][52] and renal function 49,[52][53][54][55][56][57] in healthy humans. These investigations [45][46][47][48][49][50][51][52] agree on indicating that inhibition of NO synthesis results in hemodynamic changes qualitatively similar to those observed in the current study, i.e., increments of MAP and systemic vascular resistance and reductions in cardiac output, heart rate, and stroke volume.…”

Concentric left ventricular remodeling in endothelial nitric oxide synthase knockout mice by chronic pressure overload

“…Interestingly, in eNOS À/À mice with heart failure diastolic dysfunction was also more marked when compared to WT mice [15]. Moreover, inhibition of basal NO production by the NOS inhibitor l-NMMA significantly impaired left ventricular diastolic filling [31]. In contrast, exogenous NO improves left ventricular relaxation in isolated ferret papillary muscle preparation [32] and in normal human subjects [33].…”

Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress: in vivo demonstration with magnetic resonance imaging

“…eNOS Ϫ/Ϫ mice are not only hypertensive but also characterized by enhanced systolic function and depressed diastolic function without LV hypertrophy (30). Moreover, inhibition of basal NO production by the NOS inhibitor N G -monomethyl-L-arginine significantly impaired LV diastolic filling (6). This suggests that NO derived from eNOS contributes to myocardial relaxation (29).…”