Gender difference in flow-induced dilation and regulation of shear stress: role of estrogen and nitric oxide.

Previous studies show that agonist-induced, nitric oxide (NO)-mediated arteriolar dilations are greater in female than in male rats. Thus we hypothesized that flow-dependent arteriolar dilation, which is in part mediated by NO, is also greater in females than in males. Gracilis muscle arterioles from 12-wk-old female and male Wistar rats were isolated, cannulated, and pressurized. At 80 mmHg of perfusion pressure, the active diameter and passive diameter (PD) of arterioles of female and male rats were 58.3 ± 3.4 and 53.2 ± 2.6 μm as well as 103.6 ± 4.0 and 115.3 ± 4.8 μm, respectively. Dilations to step increases in perfusate flow from 0 to 25 μl/min were significantly greater in arterioles of female rats and ovariectomized rats with estrogen replacement (OVE) than in male and ovariectomized female (OV) rats (98.6 ± 0.6 and 97.4 ± 1.1% vs. 72.6 ± 3.3 and 72.5 ± 3.6% of PD at 25 μl/min). Calculation of wall shear stress (WSS) revealed that the maintained WSS was significantly lower in arterioles of female than in those of male rats (∼20 vs. ∼35 dyn/cm2). After indomethacin pretreatment, N ω-nitro-l-arginine methyl ester (l-NAME; 10-4 M) eliminated flow-dependent dilation in arterioles of male and OV rats but only attenuated (by ∼50%) the responses in arterioles of female and OVE rats. In vessels of these latter two groups of rats, the remaining flow-induced dilation was completely eliminated by administration of 10-5 M Hb or 10-3 Ml-NAME. The greater flow/shear stress-induced dilation of arterioles of female rats indicates a gender difference in the regulation of WSS, which is likely to be due to the greater release of NO in female vessels requiring the chronic presence of estrogen. These findings suggest an important role for estrogen in the regulation of peripheral resistance in females.