Dopamine D2 receptor stimulation inhibits angiotensin II-induced hypertrophy in cultured neonatal rat ventricular myocytes.
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.
Li
Hong
H
Department of Pathophysiology, Second Affiliated Hospital of Harbin Medical University, China.
Shi
Sa
S
Sun
Yi-Hua
YH
Zhao
Ya-Jun
YJ
Li
Quan-Feng
QF
Li
Hong-Zhu
HZ
Wang
Rui
R
Xu
Chang-Qing
CQ
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001971:Bromocriptine / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D019332:Endothelin-1; D017448:Receptors, Dopamine D2; D000804:Angiotensin II; D001971:Bromocriptine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D006220:Haloperidol