Chronic all-trans retinoic acid treatment prevents medial thickening of intramyocardial and intrarenal arteries in spontaneously hypertensive rats.
There are in vitro data linking all-trans retinoic acid (atRA) with inhibition of hypertrophy and hyperplasia in cardiomyocytes, vascular smooth muscle cells, and fibroblasts. In the present study, we tested the hypothesis that chronic treatment with atRA may blunt the process of myocardial remodeling in spontaneously hypertensive rats (SHR). Four-week-old male SHR were treated with atRA (5 or 10 mg.kg-1.day-1) given daily for 3 mo by gavage; age- and sex-matched Wistar-Kyoto rats (WKY) and placebo-treated SHR served as controls. At the end of the treatment period, cardiac geometry and function were assessed by Doppler echocardiography. Histological examination and RIA were performed to evaluate medial thickening of intramyocardial and renal arteries, perivascular and interstitial collagen content, and atrial natriuretic peptide (ANP) and IGF-I in the heart, respectively. The novel finding of the present study is that atRA prevented hypertrophy of intramyocardial and intrarenal arteries and ventricular fibrosis. However, atRA treatment did not lower blood pressure or left ventricular weight and left ventricular weight-to-body weight ratio in SHR. atRA did not change cardiac geometry and function as assessed by Doppler echocardiography. atRA showed no influence on either ANP or IGF-I 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 and cardiac geometry and function are not changed by atRA treatment.
Lü
Lei
L
Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Rd., Shanghai 200032, People's Republic of China.
Yao
Tai
T
Zhu
Yi-Zhun
YZ
Huang
Guo-Ying
GY
Cao
Yin-Xiang
YX
Zhu
Yi-Chun
YC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004334:Drug Administration Schedule; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects* / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage*; D017540:Tunica Media / Q000187:drug effects* / Q000473:pathology
D014212:Tretinoin