Chronic L-NAME treatment preserved flow-induced dilation in both genders, mediated by endothelial prostaglandins in males and a cytochrome P-450 metabolite in females.
Does chronic NO synthesis inhibition with L-NAME alter the mechanisms of flow-induced arteriolar dilation differently in male versus female rats?
There are significant gender differences in endothelial adaptation to the lack of nitric oxide synthesis, with males relying on prostaglandins and females on cytochrome P-450 metabolites to maintain flow-induced dilation.
Flow-induced dilation of gracilis muscle arterioles was examined in both genders of control rats and rats chronically treated with N(omega)-nitro-L-arginine methyl ester (L-NAME). After L-NAME treatment (4 wk), systolic blood pressure was significantly increased compared with control, whereas the plasma concentration of nitrate/nitrite was significantly reduced. Isolated and pressurized arterioles dilated significantly in response to increases in flow (0-25 microl/min). Flow-induced dilation was comparable in arterioles of control and L-NAME-treated rats but was significantly greater in female than in male rats. L-NAME + indomethacin, which abolished flow-induced dilation in arterioles of male control rats, inhibited the dilation by only ~75% in female control rats. The residual portion of the response was eliminated by additional administration of miconazole, an inhibitor of cytochrome P-450. Indomethacin did not affect the dilation in female L-NAME-treated rats but completely inhibited the response in male L-NAME-treated rats. The indomethacin-insensitive, flow-induced dilation in female L-NAME-treated arterioles was abolished by miconazole, 6-(2-proparglyoxyphenyl)hexanoic acid, or charybdotoxin. Thus an augmented release of endothelial prostaglandins accounts for the preserved flow-induced dilation in arterioles of male rats, whereas a metabolite of cytochrome P-450 is responsible for the maintenance of flow-induced dilation in female rats, suggesting important differences in the adaptation of the endothelium of arterioles from male and female rats to the lack of nitric oxide (NO) synthesis.
Wu et al. (Fri,) conducted a other in Nitric oxide deficiency. L-NAME vs. Control rats was evaluated on Flow-induced dilation of gracilis muscle arterioles. Chronic L-NAME treatment preserved flow-induced dilation in both genders, mediated by endothelial prostaglandins in males and a cytochrome P-450 metabolite in females.