We hypothesized that potentiating the bioavailability of endothelial epoxyeicosatrienoic acids (EETs) via deletion of the gene for soluble epoxide hydrolase (sEH), or downregulation of sEH expression, enhances flow/shear stress-induced dilator responses (FID) of arterioles. Using male (M) and female (F) wild type (WT) and sEH-knockout (KO) mice, isolated gracilis muscle arterioles were cannulated and pressurized at 80 mmHg. Basal tone and increases in diameter of arterioles as a function of perfusate flow (5, 10, 15, 20 and 25 microl/min) were recorded. The magnitude of FID was significantly smaller, and associated with a greater arteriolar tone in M-WT than F-WT mice, revealing a sex-difference in FID. This sex-difference was abolished by deletion of the sEH gene, as evidenced by an enhanced FID in M-KO mice to a level comparable to those observed in F-KO and F-WT mice. These three groups of mice coincidentally exhibited an increased endothelial sensitivity to shear stress (smaller WSS50) and were hypotensive. Endothelial EETs participated in the mediation of enhanced FID in M-KO, F-KO and F-WT mice, without effects on FID of M-WT mice. Protein expression of sEH was downregulated by approximately 4-fold in vessels of F-WT compared to M-WT mice, paralleled with greater vascular EET levels that were statistically comparable to those observed in both male and female sEH-KO mice. In conclusion, sex-different regulation of sHE accounts for sex differences in flow mediated dilation of microvessels in gonadally intact mice.
        
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Qin J, Kandhi S, Froogh G, Jiang H, Meng L, Sun D, Huang A (2015) Sexually dimorphic phenotype of arteriolar responsiveness to shear stress in soluble epoxide hydrolase-knockout mice American Journal of Physiology Heart Circ Physiol
Qin J, Kandhi S, Froogh G, Jiang H, Meng L, Sun D, Huang A (2015) American Journal of Physiology Heart Circ Physiol