Heat and α1-Adrenergic Responsiveness in Human Skeletal Muscle Feed Arteries: The Role of Nitric Oxide
Sympatholysis, endothelial nitric oxide synthase, endothelial cells, shear stress, temperature
Increased local temperature exerts a sympatholytic effect on human skeletal muscle feed arteries. We hypothesized that this attenuated α(1)-adrenergic receptor responsiveness may be due to a temperature-induced increase in nitric oxide (NO) bioavailability, thereby reducing the impact of the α(1)-adrenergic receptor agonist phenylephrine (PE). Thirteen human skeletal muscle feed arteries were harvested, and wire myography was used to generate PE concentration-response curves at 37 °C and 39 °C, with and without the NO synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA). A subset of arteries (n = 4) were exposed to 37 °C or 39 °C, and the protein content of endothelial NOS (eNOS) and α(1)-adrenergic receptors was determined by Western blot analysis. Additionally, cultured bovine endothelial cells were exposed to static or shear stress conditions at 37 °C and 39 °C and assayed for eNOS activation (phosphorylation at Ser(1177)), eNOS expression, and NO metabolites [nitrate + nitrite (NOx)]. Maximal PE-induced vasocontraction (PE(max)) was lower at 39 °C than at 37 °C [39 ± 10 vs. 84 ± 30% maximal response to 100 mM KCl (KCl(max))]. NO blockade restored vasocontraction at 39 °C to that achieved at 37 °C (80 ± 26% KCl(max)). Western blot analysis of the feed arteries revealed that heating increased eNOS protein, but not α(1)-adrenergic receptors. Heating of bovine endothelial cells resulted in greater shear stress-induced eNOS activation and NOx production. Together, these data reveal for the first time that, in human skeletal muscle feed arteries, NO blockade can restore the heat-attenuated α(1)-adrenergic receptor-mediated vasocontraction and implicate endothelium-derived NO bioavailability as a major contributor to heat-induced sympatholysis. Consequently, these findings highlight the important role of vasodilators in modulating the vascular response to vasoconstrictors.
Journal of Applied Physiology
Ives SJ, Andtbacka RH, Kwon SH, Shiu YT, Ruan T, Noyes RD, Zhang QJ, Symons JD, Richardson RS. Heat and α1-adrenergic responsiveness in human skeletal muscle feed arteries: the role of nitric oxide. J Appl Physiol (1985). 2012 Dec 1;113(11):1690-8. doi: 10.1152/japplphysiol.00955.2012. Epub 2012 Oct 4. PubMed PMID: 23042905; PubMed Central PMCID: PMC3544510.