Effect of acidosis on contraction of microvascular smooth muscle by alpha 1- and alpha 2-adrenoceptors. Implications for neural and metabolic regulation.

Our previous studies have identified that adrenergic regulation of large arterioles and venules in skeletal muscle uses both postjunctional alpha 1- and alpha 2-adrenoceptors, whereas terminal arterioles appear to be subserved primarily by alpha 2-receptors. Adrenergic constriction of terminal arterioles is known to be particularly susceptible to inhibition by increased tissue metabolic rate. The purpose of this study was to examine the influence of tissue acidosis on alpha 1- and alpha 2-adrenoceptor constriction of skeletal muscle microvessels to determine if this differential receptor distribution might have significance in neural-metabolic interactions. Intravital microscopy of rat cremaster skeletal muscle was used to obtain concentration-response curves (diameter changes) of large distributing arterioles (mean diameter, 100 microns), small precapillary arterioles (20 microns), and capacitance venules (150 microns) for addition to the tissue bath of alpha-adrenergic agonists during normal pH (7.4) and during tissue bath acidosis (pH 7.1) produced by increasing bath PCO2. The following alpha-agonists were used: phenylephrine (alpha 1), B-HT 933 (alpha 2), and norepinephrine (mixed alpha 1/alpha 2). Acidosis had no effect on baseline diameter of the three vessel types, indicating a lack of effect on "intrinsic tone." Acidosis also had no effect on large microvessel sensitivity to phenylephrine but markedly reduced responses to B-HT 933. Acidosis had no effect on large arteriolar and venular sensitivity to norepinephrine but markedly decreased (x300) small precapillary arteriolar sensitivity. These data suggest that 1) alpha 2- but not alpha 1-adrenoceptor-mediated constriction of microvessels may be selectively sensitive to modest reductions in tissue pH, and 2) the prevalence of alpha 2-receptors on terminal arterioles and the marked sensitivity of alpha 2 constriction to tissue acidosis may contribute to the particular susceptibility of neural constriction at this level of the microcirculation to metabolic inhibition.