Mesenteric artery vasomotor function in normotensive and hypertensive rats

Abstract

Endothelium-derived hyperpolarizing factor (EDHF) contributes to vascular dilation but its chemical identity is unknown. Decreased EDHF-mediated dilation, assessed with inhibited prostaglandin and nitric oxide production, may lead to impaired vasomotion in spontaneously hypertensive rats (SHR). Mesenteric arteries were excised from SHR and normotensive (WKY) rats and myography was performed. Vessels were incubated with 3μM of the β-blocker propranolol, pre-contracted with norepinephrine, and cumulative dose-response curves for acetylcholine (Ach) were conducted. The Ach response was impaired in SHR compared to WKY (63±4% vs 95±9%, p=0.0021). 0.3mM of the nitric oxide inhibitor Nω-nitro-L-arginine (L-NAME) reduced the Ach response in SHR (20±4%, p<0.0001) whereas 5μM of the cyclooxygenase inhibitor indomethacin (INDO) improved the Ach response in SHR (83±4%, p=0.0019). Incubation with both inhibitors improved the Ach response over L-NAME alone in SHR (47±6% vs 20±4%, p=0.0003). The Ach response in WKY was not altered by INDO or L-NAME. Incubation with both inhibitors reduced the Ach response in SHR (47±6%, p=0.0268) but did not alter WKY. Reduced EDHF may contribute to SHR vascular dysfunction and future studies will aim to identify the specific EDHF contributing to altered vasomotion. Funding: Natural Sciences and Engineering Research Council of Canada and the Heart and Stroke Foundation of Ontario