Angiotensin II induced upregulation of G alpha q/11, phospholipase C beta 3 and extracellular signal-regulated kinase 1/2 via angiotensin II type 1 receptor.
BACKGROUND
The role of the G alpha q/11-mediated signal transduction pathway in angiotensin II (AngII) induced cardiac hypertrophy remains unclear. This study was to investigate the role of the G alpha q/11 signal transduction pathway in the development of cardiac hypertrophy in 2K1C hypertensive rats and in cultured neonatal rat ventricular myocytes (NRVMs) and to elucidate the effects of the pathway on AngII induced cardiac hypertrophy.


METHODS
Renal hypertension was induced in 2K1C hypertensive rats by placing a silver clip around the left renal artery. At 8 weeks after operation, the systolic blood pressure, the ratio of left ventricular weight to body weight (LV/BW), and the concentration of AngII in the heart were measured. The protein levels of G alpha q/11 and extracellular signal-regulated kinase 1/2 (ERK1/2) were assayed by Western blot analysis, and the activity of phospholipase C (PLC) in the myocardium was detected using [(3)H]-PIP2 as a substrate. Changes in [(3)H]-leucine incorporation and in the protein levels of the signal molecules G alpha q/11, PLC beta 3, and ERK1/2 were measured after NRVMs were stimulated with 10(-7) mol/L AngII.


RESULTS
The protein levels of G alpha q/11 and ERK1/2 in the hearts of 2K1C rats increased by 35.8% and 31.9%, respectively, compared with the sham group. The PLC activity in the 2K1C group was also significantly increased (P < 0.05). The levels of G alpha q/11, PLC beta 3, and ERK1/2 increased significantly after NRVMs were stimulated by AngII. The upregulation of G alpha q/11, PLC beta 3 and ERK1/2 in NRVMs occurred prior to [(3)H]-leucine incorporation increases, and could be inhibited with losartan.


CONCLUSIONS
AngII can initiate cardiac hypertrophy and upregulate signal molecules in the G alpha q/11-mediated signal transduction pathway, such as G alpha q/11, PLC beta 3 and ERK1/2, at both tissue and cellular levels.
Bai
Hua
H
Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, China.
Wu
Li-ling
LL
Xing
Dong-qi
DQ
Liu
Jie
J
Zhao
Ya-li
YL
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D002478:Cells, Cultured; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D006973:Hypertension / Q000150:complications; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D054799:Phospholipase C beta; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*; D015854:Up-Regulation
D007527:Isoenzymes; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518041:Plcb3 protein, rat; D043802:GTP-Binding Protein alpha Subunits, Gq-G11