JOURNAL ARTICLE

Dopamine D2 receptor stimulation inhibits angiotensin II-induced hypertrophy in cultured neonatal rat ventricular myocytes

Hong Li, Sa Shi, Yi-Hua Sun, Ya-Jun Zhao, Quan-Feng Li, Hong-Zhu Li, Rui Wang, Chang-Qing Xu
Clinical and Experimental Pharmacology & Physiology 2009, 36 (3): 312-8
18986329
1. Myocardial hypertrophy is a common pathological change that accompanies cardiovascular disease. Dopamine D2 receptors have been demonstrated in cardiovascular tissues. However, the pathophysiological involvement of D2 receptors in myocardial hypertrophy is unclear. Therefore, the effects of the D2 receptor agonist bromocriptine and the D2 receptor antagonist haloperidol on angiotensin (Ang) II- or endothelin (ET)-1-induced hypertrophy of cultured neonatal rat ventricular myocytes were investigated in the present study. 2. Protein content and protein synthesis, determined by examining [(3)H]-leucine uptake, were used as estimates of cardiomyocyte hypertrophy. The expression of D2 receptor protein in neonatal rat ventricular myocytes was determined using western blotting. Changes in [Ca(2+)](i) in cardiomyocytes were observed by laser scanning confocal microscopy. 3. Angiotensin II and ET-1, both at 10 nmol/L, induced myocyte hypertrophy, as demonstrated by increased protein content and synthesis, [Ca(2+)](i) levels, protein kinase C (PKC) activity and phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase and mitogen-activated protein kinase (MAPK) p38 (p38). Concomitant treatment of cells with 10 nmol/L AngII plus 10 micromol/L bromocriptine significantly inhibited cardiomyocyte hypertrophy, MAPK phosphorylation and PKC activity in the membrane, as well as [Ca(2+)](i) signalling pathways, compared with the effects of AngII alone. In addition, 10 micromol/L bromocriptine significantly inhibited cardiomyocyte hypertrophy induced by 10 nmol/L ET-1. However, pretreatment with haloperidol (10 micromol/L) had no significant effects on cardiomyocyte hypertrophy induced by either AngII or ET-1. 4. In conclusion, D2 receptor stimulation inhibits AngII-induced hypertrophy of cultured neonatal rat ventricular myocytes via inhibition of MAPK, PKC and [Ca(2+)](i) signalling pathways.

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