Endothelin-A-Mediated Vasoconstriction during Exercise with Advancing Age
Aging, arterial, blood, endothelin-1, exercise, blood p, flow, ressure
The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ET(A)) receptor. However, the regulatory influence of ET(A)-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 years; n = 9 old, 70±2 years), we examined leg blood flow, mean arterial pressure, leg arterial-venous oxygen (O2) difference, and leg O2 consumption (VO2) at rest and during knee-extensor exercise before and after intra-arterial administration of the ET(A) antagonist BQ-123. During exercise, BQ-123 administration increased leg blood flow to a greater degree in the old (+29±5 mL/min/W) compared with the young (+16±3 mL/min/W). The increase in leg blood flow with BQ-123 was accompanied by an increase in leg VO2 in both groups, suggesting a reduced efficiency following ET(A) receptor blockade. Together, these findings have identified an age-related increase in ET(A)-mediated vasoconstrictor activity that persists during exercise, suggesting an important role of this pathway in the regulation of exercising skeletal muscle blood flow and maintenance of arterial blood pressure in the elderly.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Barrett-O'Keefe Z, Ives SJ, Trinity JD, Morgan G, Rossman MJ, Donato AJ, Runnels S, Morgan DE, Gmelch BS, Bledsoe AD, Richardson RS, Wray DW. Endothelin-A-mediated vasoconstriction during exercise with advancing age. J Gerontol A Biol Sci Med Sci. 2015 May;70(5):554-65. doi: 10.1093/gerona/glu065. Epub 2014 May 12. PubMed PMID: 24821105; PubMed Central PMCID: PMC4400393.