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Vasodilator and antihypertensive effects of a novel N ‐acylhydrazone derivative mediated by the inhibition of L ‐type Ca 2+ channels
Author(s) -
Pereira Sharlene Lopes,
Kummerle Arthur Eugen,
Fraga Carlos Alberto Manssour,
Barreiro Eliezer Jesus,
Sudo Roberto Takashi,
ZapataSudo Gisele
Publication year - 2014
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2012.01076.x
Subject(s) - chemistry , aorta , vasodilation , propranolol , medicine , endocrinology , thoracic aorta
New bioactive N ‐acylhydrazone derivatives synthesized from safrole previously have been found to promote intense vasodilation and antihypertensive activity. In this study, we describe the synthesis and the cardiovascular effects of the new N ‐acylhydrazone derivative ( E )‐ N ‐methyl‐ N ′‐(thiophen‐3‐ylmethylene)benzo[d][1,3]dioxole‐5‐carbohydrazide ( LASSB io‐1289). Thoracic aorta and left papillary muscles from W istar– K yoto ( WKY ) rats and spontaneously hypertensive rats ( SHR ) were prepared for isometric tension recording. LASSB io‐1289 promoted relaxation of endothelium‐intact and denuded aortic rings with respective p IC 50 (−log IC 50 ) values of 5.07 ± 0.09 and 4.26 ± 0.09 ( P < 0.001) for WKY rats and 5.43 ± 0.05 and 5.58 ± 0.07 ( P > 0.05) for SHR . The vasodilator activity of LASSB io‐1289 was increased in the KCl ‐contracted aorta. LASSB io‐1289 attenuated the contracture elicited by Ca 2+ in depolarized aorta from both WKY rats and SHR . In endothelium‐intact aorta from WKY rats, LASSB io‐1289‐induced relaxation was unchanged after incubation with propranolol, ZM 241385, atropine, diphenhydramine, and HOE 140, but was significantly reduced by L‐NAME and ODQ . LASSB io‐1289 decreased papillary muscles contractility only at concentrations above 200 μ m . Acute intravenous injection of LASSB io‐1289 (3 mg/kg) produced a significant hypotensive response in SHR but not in WKY rats, suggesting its antihypertensive profile. The antihypertensive effect was also observed in SHR during 14 days of intraperitoneal and oral administration. In conclusion, our data demonstrated that LASSB io‐1289 induces both endothelium‐independent vasorelaxation involving the inhibition of Ca 2+ influx through L ‐type Ca 2+ channels in aorta from WKY rats and SHR , and endothelium‐dependent relaxation mediated by the NO /cyclic GMP pathway in WKY rats.