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A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats
Published on: December 2, 2016
Caduet enhances connexin 43 phosphorylation in left ventricular and thoracic aorta of SH model rats
Xiaoyan Huang1, Junlu Yang2, Baoguo Song3
1Shaanxi Provincial Key Laboratory of Infection and Immunity Diseases, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Insights
Caduet (amlodipine and atorvastatin) improves cardiac and vascular remodeling in spontaneous hypertension by enhancing connexin 43 phosphorylation. This combination therapy shows superior efficacy compared to individual components in reducing hypertensive remodeling.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Spontaneous hypertension (SH) leads to cardiac and vascular remodeling.
- The mechanism by which Caduet (amlodipine besylate and atorvastatin calcium) improves SH remodeling is not fully understood.
- Connexin 43 (Cx43) phosphorylation is implicated in cardiovascular remodeling.
Purpose of the Study:
- To investigate if amlodipine and atorvastatin (AM + AT) improve hypertensive left ventricular and thoracic aortic remodeling by regulating Cx43 phosphorylation.
- To compare the efficacy of combined AM + AT therapy with individual components in SH rats.
Main Methods:
- Spontaneous hypertension model rats (SHR) and Wistar-Kyoto (WKY) rats were used.
- Rats were treated with control, amlodipine alone, atorvastatin alone, or AM + AT for 8 weeks.
- Left ventricular mass index (LVMI), blood pressure, lipid levels, and Cx43 (total and phosphorylated) expression in cardiac and aortic tissues were analyzed.
Main Results:
- AM + AT significantly decreased LVMI and cardiomyocyte size compared to single-drug groups.
- AM + AT inhibited total Cx43 (T-Cx43) and increased phosphorylated Cx43 (P-Cx43) in the left ventricle and thoracic aorta.
- Immunofluorescence confirmed decreased T-Cx43 and increased P-Cx43 with AM + AT treatment.
Conclusions:
- AM + AT may mitigate left ventricular and thoracic aorta remodeling in SH rats by enhancing Cx43 phosphorylation.
- Combined AM + AT therapy demonstrates superior efficacy over amlodipine or atorvastatin alone in this model.
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.
