title: Effects of a novel ACE inhibitor, 3-(3-thienyl)-l-alanyl-ornithyl-proline, on endothelial vasodilation and hepatotoxicity in l-NAME-induced hypertensive rats.
abstract: Nitric oxide (NO) is a widespread biological mediator involved in many physiological and pathological processes, eg, in the regulation of vascular tone and hypertension. Chronic inhibition of NO synthase by N(G)-nitro-l-arginine methyl ester (l-NAME) hydrochloride results in the development of hypertension accompanied by an increase in vascular responsiveness to adrenergic stimuli. Recently, we developed a novel sulfur-containing angiotensin-converting enzyme inhibitor: 3-(3-thienyl)-l-alanyl-ornithyl-proline (TOP). Our previous studies indicated a superior nature of the molecule as an antihypertensive agent in spontaneously hypertensive rats (showing the involvement of renin-angiotensin-aldosterone system) in comparison to captopril. The aim of the present study was to investigate the effect of TOP on NO pathway in l-NAME-induced hypertensive rats, and captopril was included as the standard treatment group. Treatment with both TOP (20 mg/kg) and captopril (40 mg/kg) prevented the development of hypertension in l-NAME model, but TOP showed better restoration of NO and normal levels of angiotensin-converting enzyme. In addition, in vitro vasorelaxation assay showed an improvement in endothelium-dependent vasodilation in both the cases. Further, the biochemical (malondialdehyde, alanine aminotransferase, and aspartate aminotransferase) and the histopathological effects of TOP on rat liver tissues revealed a protective nature of TOP in comparison to captopril in the l-NAME model. In conclusion, TOP at 50% lesser dose than captopril was found to be better in the l-NAME model.
authors.affiliation: Peptide Synthesis Laboratory, CSIR, Institute of Genomics and Integrative Biology, Delhi, India; Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India; Department of Physiology, Jamia Hamdard Deemed University, New Delhi, India.
authors.forename: Mahesh Kumar
authors.initials: MK
authors.lastname: Seth
authors.affiliation: Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India.
authors.forename: M Ejaz
authors.initials: ME
authors.lastname: Hussain
authors.affiliation: Peptide Synthesis Laboratory, CSIR, Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Pasha
authors.affiliation: Department of Physiology, Jamia Hamdard Deemed University, New Delhi, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fahim
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C000613149:3-(3-thienyl)-l-alanyl-ornithyl-proline; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D009842:Oligopeptides; D009569:Nitric Oxide; D002216:Captopril; D019331:NG-Nitroarginine Methyl Ester
keywords: ACE inhibitor; nitric oxide