EFFECT OF REDUCED BLOOD-FLOW ON ALPHA-1-ADRENORECTOR AND ALPHA-2-ADRENOCEPTOR CONSTRICTION OF RAT SKELETAL-MUSCLE MICROVESSELS

Adrenergic constriction of skeletal muscle arterioles, particularly small terminal arterioles, is opposed by decreased blood flow or increased metabolic rate. Our previous studies indicate that neural constriction of large arterioles, which have both postjunctional alpha-1- and alpha-2-adrenoceptors, is mediated by alpha-1-receptors; small arterioles depend on alpha-2-receptors. Also, alpha-2, but not alpha-1, constriction is reduced by acidosis. Differential sensitivity of alpha-1 versus alpha-2 constriction to metabolic signals such as H+ may underlie the sensitivity of arteriolar adrenergic constriction to metabolic inhibition. To examine this hypothesis, we studied the effect of reduced perfusion on alpha-1- versus alpha-2-mediated constriction of large arterioles and venules. Intravital microscopy of rat cremaster skeletal muscle was used to obtain concentration-response curves for phenylephrine (alpha-1-agonist) and UK-14,304 (alpha-2-agonist). Thirty percent reduction in cremasteric artery flow by venous outflow obstruction had no effect on baseline diameter, indicating no effect on "intrinsic tone." Reduced perfusion also had no effect on arteriolar or venular sensitivity to phenylephrine or venular sensitivity to UK-14,304 but significantly attenuated arteriolar response to UK-14,304. To examine a possible mechanism for the selective inhibition of alpha-2 constriction by acidosis, we determined the effect of acidosis on the partial alpha-1-agonist St587. Like alpha-2 constriction, St587-mediated constriction of arterioles was reduced during acidosis and was attenuated by nifedipine. These data suggest that 1) increased local concentrations of tissue metabolites during reduced perfusion may attenuate neural constriction of small arterioles because of their reliance on alpha-2-receptors and sensitivity of alpha-2 constriction to metabolic inhibition, 2) the selective sensitivity of arteriolar alpha-2 constriction to H+ and possibly to other metabolites may be due to the reliance of alpha-2 constriction on nifedipine-sensitive calcium channels, and 3) venular alpha-2 constriction is less sensitive to metabolic regulation.