Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects.

摘要: Angiotensin (Ang) II has two major receptor isoforms, AT1 and AT2. Currently, antagonists are undergoing clinical trials in patients with cardiovascular diseases. Treatment causes elevation of plasma Ang which selectively binds to AT2 exerts as yet undefined effects. Cardiac level is low adult hearts, whereas its distribution ratio increased during cardiac remodeling action enhanced by application antagonists. Although knock-out mice sensitivity the pressor was increased, underlying mechanisms remain undefined. Here, we report unexpected finding that cardiac-specific overexpression gene using alpha-myosin heavy chain promoter resulted decreased AT1-mediated chronotropic actions. protein undetectable hearts wild-type overexpressed atria ventricles transgenic (TG) proportions relative were 41% 45% ventricles. No obvious morphological change observed myocardium there no significant difference development or heart body weight between TG mice. Infusion caused a significantly attenuated increase blood pressure response completely blocked pretreatment antagonist. This II-induced mainly due AT2-mediated strong negative effect exerted circulating physiological range did not stimulate catecholamine release. Isolated perfused Langendorff apparatus also showed responses effects on left ventricular dp/dt max values, activity mitogen-activated kinase inhibited transient outward K+ current recorded cardiomyocytes from influenced activation, this study suggested decreases pacemaker cells II. Our results demonstrate stimulation cardia novel antipressor inhibiting effects, diseases beneficial pharmacotherapeutic stimulating