{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:21:57Z","timestamp":1790421717666,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-142467"],"award-info":[{"award-number":["MOP-142467"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2017-04116"],"award-info":[{"award-number":["RGPIN-2017-04116"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic hypertension is a major risk factor for the development of cardiovascular disease and is often associated with endothelial dysfunction. KCa2.3 and KCa3.1 channels are expressed in the vascular endothelium and contribute to stimulus-evoked vasodilation. We hypothesized that acute treatment with SKA-31, a selective activator of KCa2.x and KCa3.1 channels, would improve endothelium-dependent vasodilation and transiently lower mean arterial pressure (MAP) in male, spontaneously hypertensive rats (SHRs). Isolated vascular preparations exhibited impaired vasodilation in response to bradykinin (i.e., endothelial dysfunction) compared with Wistar controls, which was associated with decreased bradykinin receptor expression in mesenteric arteries. In contrast, similar levels of endothelial KCa channel expression were observed, and SKA-31 evoked vasodilation was comparable in vascular preparations from both strains. Addition of a low concentration of SKA-31 (i.e., 0.2\u20130.3 \u03bcM) failed to augment bradykinin-induced vasodilation in arteries from SHRs. However, responses to acetylcholine were enhanced. Surprisingly, acute bolus administration of SKA-31 in vivo (30 mg\/kg, i.p. injection) modestly elevated MAP compared with vehicle injection. In summary, pharmacological targeting of endothelial KCa channels in SHRs did not readily reverse endothelial dysfunction in situ, or lower MAP in vivo. SHRs thus appear to be less responsive to endothelial KCa channel activators, which may be related to their vascular pathology.<\/jats:p>","DOI":"10.3390\/ijms20143481","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T02:23:16Z","timestamp":1563243796000},"page":"3481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacological Targeting of KCa Channels to Improve Endothelial Function in the Spontaneously Hypertensive Rat"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-6342","authenticated-orcid":false,"given":"Rayan","family":"Khaddaj Mallat","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-6176","authenticated-orcid":false,"given":"Cini","family":"Mathew John","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh C","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan J","family":"Kendrick","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7739-5325","authenticated-orcid":false,"given":"Andrew P","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","article-title":"Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries","volume":"134","author":"Mills","year":"2016","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1161\/JAHA.118.008888","article-title":"Trends in Prevalence and Control of Hypertension According to the 2017 American College of Cardiology\/American Heart Association (ACC\/AHA) Guideline","volume":"7","author":"Dorans","year":"2018","journal-title":"J. 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