{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:32:33Z","timestamp":1791592353951,"version":"4.3.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["HCP0010"],"award-info":[{"award-number":["HCP0010"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SB\/YS\/LS-40\/2014-17"],"award-info":[{"award-number":["SB\/YS\/LS-40\/2014-17"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The current study presents the novel angiotensin II receptor blocker fluorophenyl benzimidazole (FPD) as an antihypertensive agent in the SHR model of hypertension. We investigated the role of cGMP, voltage-dependent L-type calcium channels, and BK<jats:sub>Ca<\/jats:sub> channels in the vasorelaxant mechanisms of FPD in the rat superior mesenteric artery.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The antihypertensive effect of FPD was examined using an invasive technique measuring blood pressure in SHR animals. Using a myograph, tension measurement was completed in the superior mesenteric artery to elucidate the mechanisms of vasorelaxation involving AT1 receptors, the NO\/cGMP pathway, L-type calcium channels, and BK<jats:sub>Ca<\/jats:sub> channels. Ion flux (Ca<jats:sup>2+<\/jats:sup>, K<jats:sup>+<\/jats:sup>) studies were conducted in aortic smooth muscle cells. Putative targets proteins were determined by <jats:italic>in silico<\/jats:italic> docking studies. A safety evaluation of FPD was carried out using Swiss albino mice.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> FPD significantly decreased blood pressure in SHR. It relaxed superior mesenteric arteries in a concentration-dependent manner and significantly inhibited angiotensin II-induced contraction. The relaxation response was also mediated by an increase in tissue cGMP levels, inhibition of L-type calcium channels, and the opening of BK<jats:sub>Ca<\/jats:sub> channels. FPD further enhanced efflux of K<jats:sup>+<\/jats:sup> and inhibited Bay K8644-stimulated Ca<jats:sup>2+<\/jats:sup> influx in aortic smooth muscle cells and docked well in an <jats:italic>in silico<\/jats:italic> study with the targets. It was well tolerated in the toxicity study.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present study reports the antihypertensive activity of novel AT-1 receptor blocker FPD at 50 and 100\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> with cGMP, L-type calcium channels, and BK<jats:sub>Ca<\/jats:sub> channels as putative targets of vasorelaxation, and was found safe in oral toxicity.<\/jats:p>","DOI":"10.3389\/fphar.2021.611109","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T10:15:50Z","timestamp":1617099350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Antihypertensive Effect of a Novel Angiotensin II Receptor Blocker Fluorophenyl Benzimidazole: Contribution of cGMP, Voltage-dependent Calcium Channels, and BKCa Channels to Vasorelaxant Mechanisms"],"prefix":"10.3389","volume":"12","author":[{"given":"Hina","family":"Iqbal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit Kumar","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarfaraz","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Shafiq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feroz","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Hanif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind Singh","family":"Negi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debabrata","family":"Chanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5414","DOI":"10.1038\/s41598-019-41984-7","article-title":"3D-QSAR, Docking, ADME\/Tox studies on Flavone analogs reveal anticancer activity through Tankyrase inhibition","volume":"9","author":"Alam","year":"2019","journal-title":"Sci. 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