ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice.
There is increasing evidence that the renin-angiotensin system may play a important role in cardiac hypertrophy. To assess the role of angiotensin II in the induction of cardiac hypertrophy, three groups of adult mice were subjected to left ventricular pressure overload by transverse aortic constriction (TAC). For the next 7 days the groups received either the specific angiotensin II subtype 1 receptor (AT1) antagonist (losartan, 1.05 g/l; n = 17), an angiotensin enzyme inhibitor (captopril, 2 g/l; n = 17), or no treatment (n = 22) administered in the drinking water and compared with three similarly treated sham-operated groups (n = 7 each). TAC resulted in a significant increase in heart weight-to-body weight ratio (0.634 +/- 0.087 vs. 0.525 +/- 0.039, g/g x 100, P < 0.05), which was prevented by losartan (0.506 +/- 0.069, g/g x 100, P < 0.0001) despite similar hemodynamic load (proximal systolic pressure 146 +/- 31 vs. 136 +/- 32 mmHg, untreated vs. losartan, P = NS). Proximal systolic pressure was positively correlated with the development of ventricular hypertrophy. In the presence of AT1-receptor blockade, the increase in heart weight-to-body weight ratio at any given systolic pressure was significantly attenuated compared with untreated TAC mice. The increase in heart weight-to-body weight ratio was also significantly attenuated by captopril compared with untreated banded controls (0.542 +/- 0.091, g/g x 100, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Rockman
H A
HA
Department of Medicine, University of California San Diego School of Medicine, La Jolla 92093.
Wachhorst
S P
SP
Mao
L
L
Ross
J
J
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology* / Q000517:prevention & control*; D003250:Constriction; D015870:Gene Expression / Q000187:drug effects*; D006352:Heart Ventricles; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D051379:Mice; D008810:Mice, Inbred C57BL; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D009320:Atrial Natriuretic Factor; D002216:Captopril; D019808:Losartan