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 par t mediated by NO, is also greater in females than in males. Gracilis m uscle arterioles from 12-wk-old female and male Wistar rats were isola ted, cannulated, and pressurized. At 80 mmHg of perfusion pressure, th e active diameter and passive diameter (PD) of arterioles of female an d male rats were 58.3 +/- 3.4 and 53.2 +/- 2.6 mu m as well as 103.6 /- 4.0 and 115.3 +/- 4.8 mu m, respectively. Dilations to step increas es in perfusate flow from 0 to 25 mu l/min were significantly greater in arterioles of female rats and ovariectomized rats with estrogen rep lacement (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 mu l/min). Calculation of wall shear stress (WSS) revealed that the maintained WSS was significantly lower in arterioles of female than i n those of male rats (similar to 20 vs. similar to 35 dyn/cm(2)). Afte r indomethacin pretreatment, N-omega-nitro-L-arginine methyl ester (L- NAME; 10(-4) M) eliminated flow-dependent dilation in arterioles of ma le and OV rats but only attenuated (by similar to 50%) the responses i n arterioles of female and OVE rats. In vessels of these latter two gr oups of rats, the remaining flow-induced dilation was completely elimi nated by administration of 10(-5) M Hb or 10(-3) M L-NAME. The greater flow/shear stress-induced dilation of arterioles of female rats indic ates 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 ch ronic presence of estrogen. These findings suggest an important role f or estrogen in the regulation of peripheral resistance in females.