Haemodynamic and sympathetic effects of inhibition of nitric oxide synthase by systemic infusion of NG-monomethyl-L-arginine into humans are dose dependent

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Abstract

Background

In several animal species, nitric oxide (NO) buffers central neural sympathetic outflow, but data concerning humans are sparse and conflicting. We hypothesized that these conflicting results could be related to large differences in the dose of NG-monomethyl-L-arginine, a stereospecific inhibitor of NO synthase, infused in these human studies.

Objective

To investigate the haemodynamic and sympathetic effects of systemic inhibition of NO synthase by intravenous infusion of two different doses of NG-monomethyl-L-arginine into healthy humans and compare these effects with those of an equipressor dose of the non-endothelium-dependent vasoconstrictor phenylephrine.

Methods

Muscle sympathetic nerve activity was measured by microneurography and blood flow by venous occlusion plethysmography. NG-monomethyl-L-arginine was infused over 15 min at a rate of 50 μg/kg per min into members of one group (n = 8) and at a rate of 450 μg/kg per min into members of another group (n = 7). An equipressor dose of phenylephrine was infused into four subjects from each group.

Results

Infusions of NG-monomethyl-L-arginine and of phenylephrine at the higher dose similarly suppressed sympathetic activity. In contrast, infusions of NG-monomethyl-L-arginine and of an equipressor dose of phenylephrine at the lower dose had different sympathetic effects. Burst frequency of muscle sympathetic nerve activity remained unchanged during infusion of NG-monomethyl-L-arginine but decreased by roughly 50% during infusion of phenylephrine. Infusion of NG-monomethyl-L-arginine at both doses did not alter forearm blood flow. Only infusion of NG-monomethyl-L-arginine at the higher dose increased forearm vascular resistance.

Conclusions

Haemodynamic and sympathetic effects of inhibition of NO synthase by infusion of NG-monomethyl-L-arginine into humans are dose dependent. At higher doses, NG-monomethyl-L-arginine exerts sympatho-inhibitory effects that are comparable to those evoked by a non-specific vasoconstrictor drug, whereas at lower doses, it exerts sympatho-excitatory effects.

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