Author + information
- Received August 8, 1995
- Revision received October 31, 1995
- Accepted November 14, 1995
- Published online April 1, 1996.
- Ken-Ichiro Ichikawa, MD*,
- Chiaki Hidai, MD*,†,
- Chikako Okuda, MD*,
- Shin-Ichi Kimata, MD*,
- Rumiko Matsuoka, MD*,
- Saichi Hosoda, MD*,
- Thomas Quertermous, MD† and
- Masatoshi Kawana, MD*,*
- ↵*Address for correspondence: Dr. Masatoshi Kawana, The Heart Institute of Japan, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162, Japan.
Objectives. We investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions.
Background. Endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture.
Methods. We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group).
Results. The ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus FR139317. The right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus FR139317 than in those treated with monocrotaline alone (p < 0.01). As a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. This ratio was increased in all monocrotaline-treated rats but was lower (p < 0.01) in rats given monocrotaline plus FR139317 than in those given monocrotaline alone. The isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by S1 nuclease mapping also was lower (p < 0.025) in rats receiving monocrotaline plus FR139317 than in those receiving monocrotaline alone.
Conclusions. These data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.
This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Science and Culture, Tokyo, Japan. The ETA receptor antagonist FR139317 was supplied by Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
- Received August 8, 1995.
- Revision received October 31, 1995.
- Accepted November 14, 1995.
- American College of Cardiology