YM598, an Orally Active ETA Receptor Antagonist, Ameliorates the Progression of Cardiopulmonary Changes and Both-side Heart Failure in Rats with Cor Pulmonale and Myocardial Infarction
| Autor: | Takashi Miyauchi, Katsutoshi Goto, Satoshi Sakai, Masanao Sanagi, Katsumi Sudoh, Iwao Yamaguchi, Motoyuki Iemitsu, Akira Fujimori, Hironori Yuyama, Hisataka Shikama |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Endothelin A Receptor Antagonists Hypertension Pulmonary Myocardial Infarction Administration Oral Pulmonary Heart Disease Right ventricular hypertrophy Ventricular hypertrophy Internal medicine medicine Animals Myocardial infarction Rats Wistar Ligation Heart Failure Pharmacology Sulfonamides Monocrotaline business.industry Hemodynamics Cardiovascular Agents Receptor Endothelin A medicine.disease Coronary Vessels Pulmonary hypertension Bosentan Rats Disease Models Animal Preload Pyrimidines medicine.anatomical_structure Ventricle Anesthesia Heart failure Disease Progression Cardiology Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 44:S354-S357 |
| ISSN: | 0160-2446 |
| Popis: | The effects of the novel, selective endothelin-A (ET A ) receptor antagonist YM598 on both-side heart failure were investigated. Right-side heart failure secondary to pulmonary hypertension was produced by a single subcutaneous injection of 60 mg/kg monocrotaline, and post-ischemic congestive left-side heart failure (CHF) produced by surgical left coronary artery ligation. In right-side heart failure rats, oral YM598 (0.1 and 1 mg/kg for 4 weeks), but not bosentan (30 mg/kg), significantly inhibited the progression of pulmonary hypertension and the development of right ventricular hypertrophy. YM598 also improved hypoxemia and morphological pulmonary lesions in these rats. In CHF rats, moreover, long-term oral administration of YM598 (1 mg/kg/day for approximately 30 weeks) significantly ameliorated their poor survival rate (P < 0.05). In the measurement of cardio-hemodynamic parameters, YM598 improved the contractile/diastolic capacity of the left ventricle and the preload in the right ventricle to the levels seen in sham-operated rats. YM598 also markedly inhibited both ventricular hypertrophy and pulmonary congestion, as well as lowering high plasma brain natriuretic peptide levels in CHF rats. These findings suggest that YM598 may have a clinical benefit with regards to ameliorating the cardiopulmonary changes of right-side heart failure, and the cardiac dysfunction and mortality/morbidity of CHF. |
| Databáze: | OpenAIRE |
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