Alpha2-adrenoceptors can be found both on vascular smooth muscle cells and on the endothelium, where they exert opposing effects on vascular tone. In vitro, the stimulation of α2-adrenoceptors on endothelial 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 α2-adrenoceptor antagonist yohimbine (YO, 10−10−10−6 mol) on noradrenaline (NA, 10−12−10−8 mol)-induced vasoconstriction in the forearm skin microcirculation of 16 healthy volunteers 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 (AUC).
NA (10−8–10−12 mol) caused a marked, dose-dependent reduction in blood flow (mean effect − 745 ± 84 AUC PU;P< 0.001 versus saline). NA-induced vasoconstriction was enhanced by L-NMMA (mean effect − 916 ± 72 AUC PU;P< 0.001 versus NA). YO (10−6–10−10 mol) induced a significant, dose-dependent vasodilation (mean effect + 446 ± 110 AUC PU;P< 0.05 versus control); high doses of YO (10−6 mol) inhibited NA constriction (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 presence of L-NMMA, YO (10−8 and 10−10 mol) further potentiated NA-induced vasoconstriction (mean effect − 1165 ± 108 AUC PU; NS versus NA).
These data demonstrate, that in humans in vivo, endogenous NO attenuates noradrenergic constriction. The effects of YO suggest that endothelial α2-adrenoceptors are involved in the release of NO and other vasodilating substances. Furthermore, there is an additive NO-independent vasodilation, which can be unmasked by L-NMMA.