Myogenic Constriction Is Not Dependent On Endothelium In Arcuate And Mesenteric Arteries Of Normotensive And Hypertensive Rats

BackgroundMyogenic response (MR) is defined as contraction of small arteries in response to increased intraluminal pressure. Impaired MR is associated with hypertension and Chronic Kidney Disease (CKD). MR has been shown to be regulated by endothelium (ENDO) through production of vasodilators and vasoconstrictors which are differentially produced in different vascular beds. Despite this evidence, there are conflicting literature reports on the dependency of MR on ENDO. This dependency was never investigated in arcuate and mesenteric arteries of normotensive and hypertensive rats. We hypothesized that MR is dependent on ENDO and removing ENDO abolishes MR in arcuate and mesenteric arteries of Wistar Kyoto (WKY, normotensive) and Spontaneously Hypertensive Rats (SHR, hypertensive) rats.MethodsArteries were mounted in a pressure myograph chamber (PMC) filled with oxygenated Hank Balance Salt Solution (HBSS) to create a blind sac and allowed 30 min to equilibrate. Intact vascular smooth muscle cell (VSMC) and ENDO layers were evaluated by addition of a pre‐determined median effective dose of phenylephrine (0.2 μM) and carbachol (10 μM) respectively. MR was measured in response to step‐wise increases in intraluminal pressure from 80 to 180 mmHg (20 mmHg increments, 5 min each) (E‐intact MR). The arteries were then transferred into a petri dish containing human hair and moved through the length of the hair 5 times to remove ENDO (Osol et al., 1989). The vessels were re‐mounted, HBSS was flushed through the arteries for 5 mins, and blind sac was re‐created. Phenylephrine and carbachol were added and MR was re‐measured (E‐removed MR). Physical absence of ENDO was further assessed by Scanning Electron Microscopy (SEM).ResultsAll arteries contracted to phenylephrine before and after ENDO removal and did not relax significantly to carbachol after ENDO removal. SEM micrographs showed complete physical absence of the ENDO. MC in E‐removed vessels were not significantly different from MC in E‐intact in mesenteric and arcuate arteries of WKY and SHR rats.ConclusionsOur study validated an ENDO removal method that was described by Osol, et al. in 1989. Additionally, MR was shown to be independent of ENDO in mesenteric and arcuate arteries of WKY and SHR rats.Support or Funding InformationThis work was supported by Canadian Institutes of Health Research grants to Dr. Jeffrey G. Dickhout (PJT148499).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.