Microvascular Effects of Local or Systemic Inhibition of Endogenous Endothelium-Derived Relaxing Factor (Nitric Oxide) Production

The objective was to investigate microvascular effects of inhibition of endogenous nitric oxide (NO) production in rabbit skeletal muscle in vivo. Intravital microscopy of the tenuissimus muscle and recording of arterial blood pressure were performed in anesthetized rabbits. Topical administration of N-monomethyl-l-arginine (l-NMMA, 10-100 μM) or i.v. infusion of N-nitro-l-arginine methyl ester (l-NAME, 1-100 mg/kg) elicited dose-dependent vasoconstriction of the skeletal muscle microvessels. During i.v, l-NAME, a dose-dependent increase in systemic blood pressure was observed. The effects of topical l-NMMA or systemic l-NAME were reversed by i.v. infusion of l-arginine (1 g/kg) but not d-arginine. Vasodilation by topical acetylcholine, but not nitroprusside or adenosine, was inhibited by l-NMMA or l-NAME. The vasodilation in response to muscle contractions induced by motor nerve stimulation as well as the vasodilator response elicited by graded perfusion pressure reductions were unaffected by l-NAME or l-NMMA administered topically. Our results indicate that endogenous NO formed from l-arginine is a modulator of resting microvascular tone in vivo, whereas under the present conditions we were unable to demonstrate a role for endogenous NO in myogenic vasodilatation or functional hyperemia.