Enhanced Release of Prostaglandins Contributes to Flow-Induced Arteriolar Dilation in eNOS Knockout Mice

Abstract

Abstract —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 altered in gracilis muscle arterioles of mice deficient in the gene for endothelial nitric oxide synthase (eNOS-KO) compared with control wild-type (WT) mice. Gracilis muscle arterioles (≈80 μm) of male mice were isolated, then cannulated and pressurized in a vessel chamber. The increases in diameter elicited by increases in perfusate flow from 0 to 10 μL/min were similar in arterioles from eNOS-KO (n=28) and WT (n=22) mice (≈20 μm at 10 μL/min flow). Removal of the endothelium eliminated flow-induced dilations in vessels of both strains of mice. N ω -nitro- l -arginine (L-NNA, 10 −4 mol/L) significantly inhibited flow-induced dilation in arterioles of WT mice by ≈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 ≈49%, whereas it completely abolished this response in arterioles of eNOS-KO mice. Simultaneous administration of INDO and L-NNA eliminated flow-induced responses in arterioles of WT mice. Dilations to carbaprostacyclin were similar at concentrations of 10 −8 and 3×10 −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, flow-induced dilation is close to normal in arterioles of eNOS-KO mice because of an enhanced release of endothelial dilator prostaglandins and suggest that this vascular adaptation may contribute to the regulation of peripheral resistance in eNOS-KO mice.