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. 1994 May;89(5):2198-203.
doi: 10.1161/01.cir.89.5.2198.

Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload

H Ito  1 , M Hiroe, Y Hirata, H Fujisaki, S Adachi, H Akimoto, Y Ohta, F Marumo
Affiliations

Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload

H Ito et al. Circulation. 1994 May.

Abstract

Background: We have recently shown that angiotensin II-induced hypertrophy of cultured rat cardiomyocytes was partially blocked by an endothelin (ET) receptor antagonist (BQ123) selective for the ETA subtype, suggesting the possible involvement of endogenous ET-1 in the mechanism of cardiac hypertrophy in vitro. In the present study, we studied the in vivo blockade effects of BQ123 on cardiac hypertrophy provoked by left ventricular overload with aortic banding in adult rats.

Methods and results: Forty rats were divided into four groups: (1) sham-operated rats without BQ123 administration, (2) rats with aortic banding without BQ123 administration, (3) sham-operated rats with BQ123 administration, and (4) rats with aortic banding with BQ123 administration. BQ123 (250 micrograms/h) was administered continuously by an osmotic pump starting 24 hours before operation. BQ123 blocked increases in the ratio of left ventricular weight to body weight and in the diameter of cardiomyocytes provoked by aortic banding at 1 week, but those blockade actions were no longer observed at 2 weeks. Skeletal alpha-actin and atrial natriuretic peptide (ANP) mRNA in the left ventricle, transcriptional markers for cardiac hypertrophy, significantly increased in the rats with aortic banding at 1 week and 2 weeks. In the rats with BQ123 administration, despite the hemodynamic overload, skeletal alpha-actin and ANP mRNA in the left ventricle remained at the control levels at 1 week; however, those blockade actions were abolished at 2 weeks. Plasma ET-1 levels increased after aortic banding, peaking at 24 hours, then returned to the basal level at 4 days. Prepro-ET-1 mRNA levels in the left ventricle also increased 24 hours after aortic banding, then declined to the basal level at 4 days.

Conclusions: These data suggest that endogenous ET-1 synthesized in the cardiovascular system plays a role in the mechanism of cardiac hypertrophy during the early phase of pressure overload in vivo.

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