Effects of adrenoreceptor activation and aging on skeletal muscle arterioles at rest and during rapid onset vasodilation

Abstract

Sympathetic nerve activity (SNA) induces arteriolar vasoconstriction via [alpha]-adrenoreceptor ([alpha]AR) activation. Whether [alpha]AR activation affects the spread of rapid onset vasodilation (ROV) in contracting muscle is unknown. Differential [alpha]AR distribution in vascular smooth muscle has been proposed to mediate functional sympatholysis, however the [alpha]AR subtype distribution in locomotor muscle is undefined. This dissertation determined: 1) the effects of constitutive [alpha]AR activation on the spread of ROV within contracting muscle, 2) the functional [alpha]AR distribution in locomotor muscle of the mouse, and 3) the influence of [alpha]AR on ROV during aging. In arterioles of the gluteus maximus muscle (GM), I tested the hypotheses that: 1) adrenoreceptor subtype distribution is heterogeneous and 2) adrenoreceptor activation modulates the spread of ROV. The left GM of young (3-month) anesthetized C57BL/6 mice were studied using intravital microscopy. Distinct anastomotic, 1A, 2A, and 3A arterioles were studied at rest and following single muscle contraction in the presence or absence of topical [alpha]AR agonists and antagonists. Functional [alpha]AR distribution differed between proximal and distal arterioles. Constitutive [alpha]AR activation inhibited the spread of ROV between regions of the GM. It also reduced the amount of ROV seen in old ([about]20-month) versus young male mice. I conclude that functional [alpha]AR are heterogeneously distributed in arteriolar networks and serve to modulate regional vasodilation.