The effects of carvedilol on cardiac structural remodeling: the role of endogenous nitric oxide in the activity of carvedilol.

Abstract

As a third-generation β-adrenergic blocker (β-blocker), carvedilol is able to reverse cardiac structural remodeling, however, its mechanism of action remains unclear. In order to investigate this mechanism, hypertension was induced in rats by unilateral renal artery narrowing. Additionally, carvedilol alone or carvedilol combined with L-NAME, a specific inhibitor of nitric oxide (NO) synthase, were administered to rats by gastric gavage for 8 weeks. Systolic blood pressure (SBP) was monitored once a week for each rat until sacrifice; the blood was kept to examine plasma NO level and the tissues were used for hematoxylin and eosin (H&E) and Masson's trichrome staining. Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were calculated to quantitatively evaluate myocardial fibrosis. Our data showed that SBP was not different between the carvedilol-treated (Car) and carvedilol combined L-NAME groups (Car+L) at 8 weeks. Carvedilol significantly suppressed myocardial fibrosis and decreased both CVF and PVCA, although L-NAME blunted the effects caused by carvedilol. These results demonstrated that the effect caused by carvedilol on cardiac remodeling is largely dependent on endogenous NO.