| Description |
Through the use of in vitro methods, previous research in animal models has attempted to isolate the effects of local metabolic factors, normally associated with exercising skeletal muscle, on vascular reactivity and thus blood flow regulation. Utilizing an in vitro vessel approach and human skeletal muscle feed arteries, the purpose of these studies was to determine if local factors, such as heat and acidosis, could alter vascular reactivity and thus contribute to reduced sympathetically induced vasoconstriction (functional sympatholysis) and exercise hyperemia. Specifically, it was hypothesized that heat and acidosis will suppress vasocontracile function in human skeletal muscle feed arteries. The first study investigated the effect of temperature on ?1- adrenergic receptor stimulation using phenylephrine (PE). Cooling to 35 °C or heating to 39 °C both resulted in an attenuated PE-induced vasocontraction, while smooth muscle function, as determined by KCl, remained unchanged. The goal of the second study was to determine if the potent vasodilator, nitric oxide (NO), could be a factor mediating the heat-induced attenuation in PE-induced contraction observed in the first study. Heating again reduced PE-induced vasocontraction, and was restored with NO blockade. Using molecular approaches, it was determined that heating did not change the density of ?1-receptors, but increased endothelial nitric oxide synthase (eNOS) protein expression. The third study sought to determine the effect of acidosis on vascular reactivity. Increasing levels of acidosis resulted in graded reductions in ?1- receptor-induced vasocontraction, which was in part due to reduced smooth muscle function as assessed by KCl. Increasing acidosis maintained maximal vasorelaxation and suggested enhanced sensitivity to both the endothelium-dependent agonist acetylcholine (ACh) and the endotheliumindependent NO donor sodium nitroprusside (SNP). Collectively, these results indicate that local factors normally associated with exercise-induced increases in skeletal muscle metabolism (i.e. heat and acidosis) are, in fact, capable of altering feed artery vascular reactivity in humans, and therefore likely play a role in sympatholysis in vivo. |
