EFFECT OF ACIDOSIS ON CONTRACTION OF MICROVASCULAR SMOOTH-MUSCLE BY ALPHA-1-ADRENOCEPTORS 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 α1- and α2-adrenoceptors, whereas terminal arterioles appear to be subserved primarily by α2-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 α1- and α2-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 μm), small precapillary arterioles (20 μm), and capacitance venules (150 μm) for addition to the tissue bath of α-adrenergic agonists during normal pH (7.4) and during tissue bath acidosis (pH 7.1) produced by increasing bath PCO2. The following α-agonists were used: phenylephrine (α1), B-HT 933 (α2), and norepinephrine (mixed α1/α2). 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) α2- but not α1-adrenoceptor-mediated constriction of microvessels may be selectively sensitive to modest reductions in tissue pH, and 2) the prevalence of α2-receptors on terminal arterioles and the marked sensitivity of α2 constriction to tissue acidosis may contribute to the particular susceptibility of neural constriction at this level of the microcirculation to metabolic inhibition.