NYMC Faculty Publications
Sexually Dimorphic Phenotype of Arteriolar Responsiveness to Shear Stress in Soluble Epoxide Hydrolase-Knockout Mice
Author Type(s)
Faculty
DOI
10.1152/ajpheart.00568.2015
Journal Title
American Journal of Physiology. Heart and Circulatory Physiology
First Page
H1860
Last Page
6
Document Type
Article
Publication Date
12-1-2015
Keywords
arterioles, epoxyeicosatrienoic acids, flow/shear stress-induced vasodilation, sex, soluble epoxide hydrolase
Disciplines
Medicine and Health Sciences
Abstract
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. With the use of 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 μl/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 with 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 fourfold in vessels of F-WT compared with M-WT mice, paralleled with greater vascular EET levels that were statistically comparable with those observed in both male and female sEH-KO mice. In conclusion, sex-different regulation of sEH accounts for sex differences in flow-mediated dilation of microvessels in gonadally intact mice.
Recommended Citation
Qin, J., Kandhi, S., Froogh, G., Jiang, H., Luo, M., 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 and Circulatory Physiology, 309 (11), H1860-6. https://doi.org/10.1152/ajpheart.00568.2015