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1 Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China
2 Department of Pharmacology, National University of Singapore, Singapore
3 The Children's Hospital, Fudan University Shanghai Medical College, Shanghai, China
* To whom correspondence should be addressed. E-mail: yczhu{at}shmu.edu.cn.
There are in vitro data linking all-trans retinoic acid (atRA) with inhibition of hypertrophy and hyperplasia in cardiomyocytes, vascular smooth muscle cells and fibroblast. In the present study, we testified the hypothesis that chronic treatment with atRA may blunt the process of myocardial remodeling in spontanously hypertensive rats (SHR). Four-week-old male SHR were treated with atRA (5mg. kg-1. d-1 or 10mg . kg-1. d-1) given daily for 3 months by gavage, age- and sex-matched Wistar-Kyoto (WKY)rats and placebo-treated SHRs were served as control. At the end of the treatment period, cardiac geometry and function was assessed by Doppler-echocardiography. Histological examination and radioimmunoassay were performed to evaluate medial thickening of intramyocardial- and renal arteries, perivascular and interstitial collagen content, and atrial natriuretic peptide (ANP) and insulin-like growth factor-1 (IGF-1) in the heart, respectively. The novel finding of the present study is that atRA prevented the hypertrophy of intramyocardial- and intrarenal arteries and ventricular fibrosis. However, atRA treatment did not lower blood pressure, nor the left ventricular weight (LVW) and left ventricular weight to body weight ratio (LVW/BW) in SHRs. atRA did not change cardiac geometry and function as assessed by Doppler-echocardiography. atRA showed no influence on either the ANP or the IGF-1 levels. In conclusion, the present study suggests that chronic atRA treatment prevents medial thickening of intramyocardial- and intrarenal arteries and ventricular fibrosis during the development of hypertension. Left ventricular hypertrophy, cardiac geometry and function are not changed by atRA treatment.
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