Chronic Hypoxia Increases Staurosporine Sensitivity of Pulmonary Artery Smooth Muscle to Endothelin-1
| Autor: | C.S. Fisher, H.G. Barthlow, W. W. Murdoch, R. A. Bialecki |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.hormone medicine.medical_specialty Pulmonary Artery Muscle hypertrophy Rats Sprague-Dawley Endothelins Internal medicine medicine.artery medicine Animals Staurosporine Pharmacology (medical) Enzyme Inhibitors Hypoxia Protein Kinase C Endothelin-1 business.industry Biochemistry (medical) Muscle Smooth Hypoxia (medical) medicine.disease Pulmonary hypertension Endothelin 1 Rats Kinetics medicine.anatomical_structure Endocrinology Ventricle Anesthesia Pulmonary artery medicine.symptom business medicine.drug |
| Zdroj: | Pulmonary Pharmacology & Therapeutics. 11:159-163 |
| ISSN: | 1094-5539 |
| Popis: | Endothelins (ET) have been implicated in the pathogenesis of hypoxia-induced pulmonary hypertension. We evaluated the contribution of protein kinase C (PKC) to the ET-1 response of isolated endothelium-denuded extralobar pulmonary artery (PA) from rats exposed to chronic hypoxia (10% O2-90% N2, 1 ATM, 14 days or 28 days) or air. Hypoxia increased hematocrit (Hct [% above air control]: at 14 days, by 28+/-2%; after 28 days to 33+/-2%) and the mass ratio of right ventricle over left ventricle plus septum (RV/LV+S [% above air control]: at 14 days, by 54+/-1%; after 28 days to 114+/-13%), an index of right ventricle hypertrophy. Hypoxic exposure for 14 days and 28 days decreased PA sensitivity to ET-1 (change in EC50: 14 days, four-fold; 28 days, two-fold vs. air controls) and transiently decreased the magnitude of maximum ET-1-induced contraction (Emax [% decrease from control]: 14 days, 53+/-6%; 28 days, 23+/-6%). Staurosporine, a PKC inhibitor, decreased ET-1 sensitivity of PA from 0, 14, and 28 days air-exposed rats by four- to nine-fold without affecting Emax. However, staurosporine markedly decreased hypoxic PA sensitivity to ET-1 (change in EC50: 14 days, 1700-fold; 28 days, 55-fold vs. hypoxic controls) and decreased Emax (% decrease from hypoxic control: 14 days, 38+/-6%; 28 days, 59+/-7%). In conclusion, hypoxic exposure time-dependently varies the responsiveness of PA smooth muscle to ET-1 and may modulate the contribution of PKC activation. |
| Databáze: | OpenAIRE |
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