Differential sensitivity of arteriolar alpha 1- and alpha 2-adrenoceptor constriction to metabolic inhibition during rat skeletal muscle contraction.

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Abstract
Our previous studies in rat skeletal muscle have determined that neural constriction of large arterioles, which regulate blood flow and peripheral resistance, is mediated by alpha 1-adrenoceptors, whereas small arterioles, which determine effective capillary density, depend on alpha 2-receptors. During physical exercise, metabolic vasodilators from contracting skeletal muscle oppose neural vasoconstriction. By mechanisms that are not understood, adrenergic constriction of small arterioles is particularly sensitive to metabolic inhibition during imbalances in oxygen supply versus demand. This sensitivity may result from the reliance of small arterioles on alpha 2-receptors and a greater sensitivity of alpha 2 constriction to metabolic dilators. We previously demonstrated selective attenuation of arteriolar alpha 2 constriction during a reduction in the oxygen supply/demand ratio subsequent to decreased skeletal muscle perfusion. In the present study, intravital microscopy of rat cremaster skeletal muscle was used to examine the effect of increased oxygen demand on adrenergic constriction of arterioles. The effect of multiple frequencies of skeletal muscle contraction (via genitofemoral nerve stimulation) on alpha 1 (norepinephrine + rauwolscine) and alpha 2 (norepinephrine + prazosin) constriction was used to evaluate neural-metabolic interactions over a wide range of metabolic conditions. Low-frequency (less than or equal to 2 Hz) skeletal muscle contraction attenuated only alpha 2 constriction; contractions greater than or equal to 4 Hz attenuated alpha 1 constriction and further reduced alpha 2 constriction. Comparison of the frequency of contraction necessary to produce inhibition of 20% of maximal dilation indicated that alpha 2 constriction was approximately 10-fold more sensitive than alpha 1 constriction to "metabolic" inhibition. High-frequency, but not low-frequency, contraction also inhibited intrinsic tone. These data suggest that release of dilator substances during moderate exercise may preferentially attenuate alpha 2 constriction to produce small arteriolar dilation and increased capillary density. In contrast, metabolic signals associated with higher frequency muscle contraction may inhibit both intrinsic tone and large arteriolar alpha 1 tone so that blood flow and oxygen delivery increase to match the elevated oxygen demand of more heavily exercising muscle.