Effects of all-trans retinoic acid on angiotensin II-induced myocyte hypertrophy.
We used cultured neonatal rat cardiac myocytes to test the hypothesis that all-trans retinoic acid (atRA) may act to modulate ANG II actions in inducing myocyte hypertrophy. Our observations were as follows. 1) atRA (10(-7) to approximately 10(-5) M ) inhibited ANG II-induced hyperplasia of fibroblasts in a dose-dependent manner. 2) Treatment of atRA attenuated the ANG II-induced increase in total cell protein content. 3) Treated with ANG II (10(-7) M) for 5 days, the cultured neonatal rat cardiac myocytes demonstrated an apparent accumulation of sarcomeric fiber proteins and Golgi's complex, as well as reorganization of the sarcomeric unit within individual myocytes. atRA (10(-6) M) treatment reduced the accumulation of contractile proteins and Golgi's complex without affecting the ANG II-induced reorganization of the sarcomeric unit. 4) atRA attenuated the ANG II-induced increase in intracellular Ca2+. Our results show that atRA inhibits some effects of ANG II on neonatal rat cardiac myocytes and suggest that atRA may be a therapeutic candidate for the prevention and therapy of cardiac hypertrophy and remodeling.
Wang
Hao-Jie
HJ
Kidney and Hypertension Research Center, Department of Physiology, Medical Center of Fudan University, Shanghai 200032, People's Republic of China.
Zhu
Yi-Chun
YC
Yao
Tai
T
D000804:Angiotensin II; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007424:Intracellular Fluid / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D011506:Proteins; D000804:Angiotensin II; D014212:Tretinoin; D002118:Calcium