Enhanced release of prostaglandins contributes to flow-induced arteriolar dilation in eNOS knockout mice

Nitric oxide and prostaglandins were shown to contribute to the endothelial mediation of flow-induced dilation of skeletal muscle arterioles of rats. Thus, we hypothesized that flow-induced dilation and its mediation are alte red in gracilis muscle arterioles of mice deficient in the gene for endothe lial nitric oxide synthase (eNOS-KO) compared with control wild-type (WT) m ice. Gracilis muscle arterioles (approximate to 80 mu m) of male mice were isolated, then cannulated and pressurized in a vessel chamber. The increase s in diameter elicited by increases in perfusate flow from 0 to 10 mu L/min were similar in arterioles from eNOS-KO (n = 28) and WT (n = 22) mice (app roximate to 20 mu m at 10 mu L/min flow), Removal of the endothelium elimin ated flow-induced dilations in vessels of both strains of mice. N-omega-nit ro-L-arginine (L-NNA, 10(-4) mol/L) significantly inhibited flow-induced di lation in arterioles of WT mice by approximate to 51% but had no effect on responses of arterioles from eNOS-KO mice. Indomethacin (INDO, 10(-5) mol/L ) inhibited flow-induced dilation of WT mice by approximate to 49%, whereas it completely abolished this response in arterioles of eNOS-KO mice, Simul taneous administration of INDO and L-NNA eliminated flow-induced responses in arterioles of WT mice. Dilations to carbaprostacyclin were similar at co ncentrations of 10(-8) and 3 x 10(-8) mol/L but decreased significantly at 10(-7) mol/L in arterioles of eNOS-KO compared with those of WT mice. These findings demonstrate that, despite the lack of nitric oxide mediation, flo w-induced dilation is close to normal in arterioles of eNOS-KO mice because of an enhanced release of endothelial dilator prostaglandins and suggest t hat this vascular adaptation may contribute to the regulation of peripheral resistance in eNOS-KO mice.