Abstract
Caduet, also known as amlodipine besylate and atorvastatin calcium (AM + AT) tablet, can improve cardiac and vascular remodeling in patients with spontaneous hypertension (SH), but the underlying mechanism remains unknown. The present study aimed to explore whether AM + AT improved hypertensive left ventricular and thoracic aortic remodeling by regulating connexin 43 (Cx43) phosphorylation. A total of 32 male spontaneous hypertension model rats (SHR) were randomly divided into four groups: SHR control group, amlodipine-alone group (SHR-AM), atorvastatin-alone (SHR-AT) and AM + AT group (SHR-AM + AT); 8 Wistar-Kyoto (WKY) rats with normal blood pressure were used as the normal control. Drugs were orally administered for 8 weeks; subsequently, body weight, heart rate (HR), left ventricular mass index (LVMI), blood pressure (BP), plasma lipid levels and morphological changes of myocardial tissue in each group were analyzed. The expression of total (T)-Cx43 and phosphorylated (P)-Cx43 protein in the left ventricular and thoracic aortic tissues was determined using western blotting and immunofluorescence double labeling. The results revealed that AM + AT significantly decreased LVMI and cardiomyocyte cross-sectional area compared with SHR-AM and SHR-AT group. The western blotting results demonstrated that AM + AT could inhibit the expression of T-Cx43 protein, but increased the expression of P-Cx43 in the left ventricular and thoracic aorta. Moreover, immunofluorescence results indicated AM + AT could also decrease the expression T-Cx43, and increase that of P-Cx43 in the left ventricular and thoracic aorta compared with AM and AT alone. Therefore, it was concluded that AM + AT may mitigate left ventricular and thoracic aorta remodeling in SH rats by enhancing Cx43 phosphorylation, and the efficacy of AM + AT was superior to that of AM and AT alone.