19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension |
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| Authors: | Rambabu Dakarapu Ramu Errabelli Vijaya L Manthati Adeniyi Michael Adebesin Deb K Barma Deepan Barma Victor Garcia Fan Zhang Michal Laniado Schwartzman John R Falck |
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| Institution: | 1. Division of Chemistry, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;2. CRO Laboratories, 9995 Monroe Drive, Suite 119, Dallas, TX 75220, USA;3. Department of Pharmacology, New York Medical College School of Medicine, Valhalla, NY 10595, USA |
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| Abstract: | 19-Hydroxyeicosatetraenoic acid (19-HETE, 1), a metabolically and chemically labile cytochrome P450 eicosanoid, has diverse biological activities including antagonism of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE, 2). A SAR study was conducted to develop robust analogs of 1 with improved in vitro and in vivo efficacy. Analogs were screened in vitro for inhibition of 20-HETE-induced sensitization of rat renal preglomerular microvessels toward phenylephrine and demonstrated to normalize the blood pressure of male Cyp4a14(-/-) mice that display androgen-driven, 20-HETE-dependent hypertension. |
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| Keywords: | Corresponding author QDEGARKRKXEQDF-AAHZGTINSA-M Antagonist Vascular sensitization Hypertension Eicosanoid Bioisosteric replacement |
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