HIGHLIGHTED TOPIC Skeletal and Cardiac Muscle Blood Flow Role of estrogen in nitric oxide- and prostaglandin-dependent modulation of vascular conductance during treadmill locomotion in rats

Rogers, Jennifer, and Don D. Sheriff. Role of estrogen in nitric oxideand prostaglandin-dependent modulation of vascular conductance during treadmill locomotion in rats. J Appl Physiol 97: 756– 763, 2004; 10.1152/japplphysiol.00115.2004.—Endothelial production of nitric oxide (NO) and prostaglandins (PG) may be greater in females than in males, increasing vasodilatory responses in females. Does sex influence the cardiovascular responses to dynamic exercise through estrogen-dependent modulation of NO and PG vasodilatory pathways? After the administration of hexamethonium, we assessed terminal aortic blood flow (TAQ), mean arterial pressure (MAP), and hindlimb vascular conductance (VC) in four groups of rats (6 males, 5 females, 5 ovariectomized females, and 6 ovariectomized females with chronic estrogen supplementation) during graded mild-intensity treadmill locomotion (5–15 m/min, 0° grade, 2 min). All rats repeated exercise after cyclooxygenase inhibition (indomethacin) and then again after NO synthase inhibition (nitro-L-arginine methyl ester) to examine the roles of NO and PG. Regression analysis was used to determine the influence of sex and plasma 17 -estradiol on TAQ, MAP, and VC. The analysis revealed that female sex did not influence TAQ but reduced MAP and increased VC at rest and during exercise conditions. Plasma 17 -estradiol (measured by immunoassay) significantly decreased MAP and increased TAQ and VC, irrespective of sex. Cyclooxygenase inhibition eliminated the significant association between MAP and estrogen, suggesting that estrogenic modulation occurred through PG-dependent processes. In contrast, the significant influence of estrogen on TAQ and VC was eliminated after NO synthase inhibition. On the basis of the overall findings of this study, estrogen influenced the vascular responses to dynamic exercise through PGand NO-dependent pathways, but this occurred independent of sex.