Phenylethanol Glycosides Protect Myocardial Hypertrophy Induced by Abdominal Aortic Constriction via ECE-1 Demethylation Inhibition and PI3K/PKB/eNOS Pathway Enhancement.

Qiong-Ling Fan,Tao Liu,Shu-Ping You,Jun Zhao,Shi-Lei Zhang,Jia-Wei Wang

doi:10.1155/2020/2957094

Abstract

Phenylethanol glycosides (CPhGs) are the core material basis of pharmacological activity in Cistanche tubulosa and have a variety of pharmacological effects. However, it is unclear whether CPhGs have an ameliorative effect on pressure overload-induced myocardial hypertrophy. In this study, male SD rats weighing (200 ± 20) g were established cardiac hypertrophy models by abdominal aortic coarctation (AAC). After operation, the rats were gavaged with corresponding medicine for 6 weeks (CPhGs 125, 250, and 500 mg/kg/d and valsartan 8.3 mg/kg/d). Echocardiography, heart weight index (HWI), cross-sectional area of cardiomyocytes (CSCA), fibrosis area, plasma endothelin 1(ET-1), and proinflammatory factors levels were detected. Our results showed that different CPhGs dosage decreased left ventricular posterior wall thickness (LVPWT), left ventricular end-diastolic diameter (LVED), HWI, CSCA, fibrosis area, ET-1, proinflammatory factors, arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin converting enzyme 1(ECE-1) mRNA levels, cyclooxygenase 2 (COX-2), high mobility group box 1 (HMGB-1) protein levels, and ECE-1 demethylation level while increasing left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-PKB), and phosphorylated endothelial nitric oxide synthetase (p-eNOS). The indexes of CPhGs 250 and 500 mg/kg group were significantly different from AAC group; compared with valsartan group (AV), the indexes of CPhGs 500 mg/kg group were not significantly different. In conclusion, CPhGs ameliorated myocardial hypertrophy rats by AAC, which may be related to ECE-1 demethylation inhibition and PI3K/PKB/eNOS enhancement.

Highlights

Myocardial hypertrophy is a common adaptive response to pressure overload in hypertensive patients [1]
Two rats died after aortic coarctation (AAC): one in model group died on the third day after AAC from pulmonary edema; another one in AC 500 mg/kg died the day after surgery suspected to be caused by surgical stress
Compared with AAC group, left ventricular end-diastolic diameter (LVED), left ventricular ejection fractions (LVEF), and left ventricular fractional shortening (LVFS) were increased and left ventricular posterior wall thickness (LVPWT) was decreased to varying degrees in each AC dose group; for LVPWT, significant change was not found in AC 125 mg/kg group but was found in AC 250 and 500 mg/kg groups

Summary

Introduction

Myocardial hypertrophy is a common adaptive response to pressure overload in hypertensive patients [1]. With the aggravation of myocardial hypertrophy, the demand for myocardial blood supply increases, and the decrease of coronary blood flow reserve leads to myocardial injury. E development of myocardial hypertrophy is known to increase the morbidity and mortality of cardiovascular diseases [2,3,4]. Since hypertension is the main cause of myocardial hypertrophy, the current treatment of myocardial hypertrophy is mainly based on antihypertensive drugs, such as thiazine diuretics, calcium channel blockers, and angiotensin-converting enzyme inhibitors [5, 6]. The electrolyte disturbance, postural hypotension, dry cough, and other adverse reactions caused by taking these drugs remain potential risks for patients. There is an urgent need to find safer and more effective drugs.

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