Interaction Between Microvascular a 1 - and a 2 - Adrenoceptors and Endothelium - Derived Relaxing Factor

Intravital microscopy was used to study the effect of endothelium-derived relaxing factor (EDRF) on microvascular adrenoceptor sensitivity in rat cremaster skeletal muscle. NG-Monomethyl L-arginine (L-NMMA, 1-300 ,uM), an inhibitor ofEDRF formation, produced concentration-dependent constriction of arterioles and venules. When an intermediate amount of a-l versus a2-adrenoceptor tone was first produced with bath-added norepinephrine (NE) in the presence of rauwolscine or prazosin, L-NMMA caused constriction with greater potency and efficacy during aY2 than during crl tone. During localized arl or aY2 constriction along an arteriole by perivascular micropipette suffusion of NE in the presence of rauwolscine or prazosin, again, bath-added L-NMMA produced constriction with greater potency during a2 than during arl constriction. Like L-NMMA, disruption of EDRF release by microembolization caused baseline arteriole constriction and selectively increased aY2 sensitivity 75-fold. Although these findings support the hypothesis that endothelial cells possess ar2-adrenoceptors that promote EDRF release, a greater susceptibility of a2 than arl constriction to EDRF inhibition could also account for the results. In support of this latter possibility, a2 constriction was approximately 50-fold more susceptible than al constriction to inhibition by the EDRF-like nitrodilator nitroprusside. The similarity in magnitude of this difference in sensitivity with the difference obtained in the embolization experiments does not support the hypothesis that microvascular endothelial cells in skeletal muscle possess EDRF-promoting av2-adrenoceptors. However, these data do suggest that endogenous EDRF release modulates basal arteriole and venule tone and that aY2-adrenoceptor constriction is more sensitive than a, constriction to inhibition by EDRF. (Circulation Research 1992;71:188-200)