The nitric oxide synthase inhibitor L-NMMA potentiates noradrenaline-induced vasoconstriction: effects of the alpha(2)-receptor antagonist yohimbine

Objective Alpha(2)-adrenoceptors can be found both on vascular smooth muscl e cells and on the endothelium, where they exert opposing effects on vascul ar tone. In vitro, the stimulation of alpha (2)-adrenoceptors on endothelia l cells leads to the release of vasodilating substances like nitric oxide ( NO) and prostanoids, Little is known of this mechanism in vivo. Design and methods We investigated the effects of the NO-synthase inhibitor L-NMMA (10(-6) mol) and the alpha (2)-adrenoceptor antagonist yohimbine (Y O, 10(-10)-10(-6) mol) on noradrenaline (NA, 10(-12)-10(-8) mol)-induced va soconstriction in the forearm skin microcirculation of 16 healthy volunteer s using double injection technique and laser Doppler flowmetry, Results are expressed in perfusion units (PU) as differences from baseline and control in mean +/- SEM; the area under the time-response-curve was calculated (AU C), Results NA (10(-8)-10(-12) mol) caused a marked, dose-dependent reduction i n blood flow (mean effect -745 +/- 84 AUC PU; P < 0.001 versus saline). NA- induced vasoconstriction was enhanced by L-NMMA (mean effect -916 <plus/min us> 72 AUC PU; P < 0.001 versus NA). YO (10(-6)-10(-10) mol) induced a sign ificant, dose-dependent vasodilation (mean effect + 446 <plus/minus> 110 AU C PU; P < 0.05 versus control); high doses of YO (10-6 mol) inhibited NA co nstriction (P < 0.001 versus NA), whereas lower doses of YO (10(-8)/10(-10) mol) had no effect or even increased NA-induced constriction. In the prese nce of L-NMMA, YO (10(-8) and 10(-10) mol) further potentiated NA-induced v asoconstriction (mean effect -1165 +/- 108 AUC PU; NS versus NA). Conclusion These data demonstrate, that in humans in vivo, endogenous NO at tenuates noradrenergic constriction. The effects of YO suggest that endothe lial alpha (2)-adrenoceptors are involved in the release of NO and other va sodilating substances. Furthermore, there is an additive NO-independent vas odilation, which can be unmasked by L-NMMA. J Hypertens 19:907-911 (C) 2001 Lippincott Williams & Wilkins.