Efficacy of CI-1020, an Endothelin-A Receptor Antagonist, in Hypoxic Pulmonary Hypertension
| Autor: | Richard L Schroeder, S. J. Haleen, Joan A. Keiser, Hussein Hallak, Edie Quenby-Brown, Donnelle M. Walker, Andrew C.G. Uprichard, Kathleen M. Welch |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Endothelin Receptor Antagonists
Male medicine.medical_specialty Hypertension Pulmonary Blood Pressure Cardiomegaly Dioxoles Peptide hormone Muscle hypertrophy Rats Sprague-Dawley Right ventricular hypertrophy medicine.artery Internal medicine medicine Animals Hypoxia Pharmacology Endothelin-1 business.industry Antagonist Hypoxia (medical) Receptor Endothelin A medicine.disease Pulmonary hypertension Rats Endocrinology Chronic Disease Pulmonary artery medicine.symptom Cardiology and Cardiovascular Medicine Endothelin receptor business |
| Zdroj: | Journal of Cardiovascular Pharmacology. 31:S331-S335 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-199800001-00092 |
| Popis: | We previously showed that CI-1020, an endothelin (ET)-A-selective receptor antagonist, dose-dependently blocked acute hypoxic pulmonary hypertension (PH) in rats. In this study we show that CI-1020 can reverse existing PH and prevent progression of right ventricular hypertrophy (RVH) in rats exposed to chronic hypoxia. Male Sprague-Dawley rats were exposed to 20 days of hypoxia (10% O2) with CI-1020 treatment (20 or 40 mg/kg/day) starting on day 10. On day 20 of hypoxia, the rats were instrumented under anesthesia with a pulmonary artery cannula and allowed to recover to consciousness before measurement of mean pulmonary arterial pressure (MPAP). Blood samples were then collected for plasma ET-1 measurements, the rats killed, and their hearts dissected, dried, and weighed. RV/LV + septum ratio (g/g) was used as an index of RVH (RVHi). Normoxic rats and rats exposed to hypoxia for only 10 days were also evaluated as controls. Normoxic rats had MPAPs of 13 +/- 1 mm Hg, plasma ET-1 levels of 2.1 +/- 0.1 pg/ml, and an average RVHi of 0.29 +/- 0.03. Rats exposed to 10 or 20 days of hypoxia had MPAPs of 33 +/- 2 and 44 +/- 0 mm Hg, plasma ET-1 levels of 4.2 +/- 0.8 and 4.6 +/- 0.8 pg/ml, and average RVHis of 0.47 +/- 0.05 and 0.52 +/- 0.03, respectively. In comparison, rats treated with CI-1020 had MPAPs that were 37% (20 mg/kg/day) and 44% (40 mg/kg/day) lower than untreated 20-day hypoxic rats. Furthermore, rats dosed with 40 mg/kg/day of CI-1020 had MPAPs that were significantly lower (24%) than control 10-day hypoxic rats, indicating a significant reversal of PH. Along with this reversal in PH, their average RVHi was 23% lower (p0.05) relative to untreated 20-day hypoxic rats. |
| Databáze: | OpenAIRE |
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