ABSTRACT
OBJECTIVE: To synthesize and evaluate of antihypertensive activity of novel nitric oxide-releasing N-phenyl-1H-pyrrole derivatives. METHODS: By connecting key structural elements present in an AT1 receptor antagonist irbesartan with N-phenyl-1H-pyrrole carboxylic acid, a novel AT1 antagonist compound 4 was designed and synthesized, and a series of novel NO-donating derivatives (IN 1-10) were obtained by introducing NO donor. The amount of NO production in vitro of the target compounds were determined by Greiss assay. And the antagonism of Ang II induced vascular contraction assay was used to value the inhibition rate. RESULTS: The antagonism of Ang II induced vascular contraction assay indicated that the novel compound exhibited similar activity as losartan. The NO derivative, compound IN9, found to release the maximum amount of NO during the NO releasing assay, was more potent than the lead compound 4 and positive control losartan. CONCLUSION: These date indicate that the improved activities of these hybrid molecules contribute to the NO donor and the protection ability of NO donor make them promising candidates as antihypertensive agents.
ABSTRACT
Objective Objective To investigate the effects of losartan on neointimal proliferation and macrophage count in neointima.Methods The rabbits underwent abdominal aorta balloon de-endothelialization,then received a 1 5 % cholesterol diet for 8 weeks.Abdominal aorta atherosclerosis model was performed in 16 rabbits.Immediately after operation, losartan was orally administered to the rabbits of the losartan group (10mg?kg -1 ?day -1 ), while the rabbits of the control group were given normal saline. Four weeks later the animals were killed and the excised artery segments were prepared for histomorphological observation and macrophages were investigated by immunohistochemistry analysis.Results Compared with the control group, the IT/MT ratio and IA/MA ratio of the losartan group were significantly reduced(P