Chronic hypoxia augments endothelin-B receptor-mediated vasodilation in isolated perfused rat lungs

Autor: Masahiko Oka, Sanae Soma, Masashi Muramatsu, Hideki Takahashi, Yoshiteru Morio, Yoshinosuke Fukuchi
Rok vydání: 1999
Předmět:
Pulmonary and Respiratory Medicine
Agonist
Male
Endothelium-derived hyperpolarizing factor
medicine.medical_specialty
Pulmonary Circulation
Potassium Channels
Physiology
medicine.drug_class
Hypertension
Pulmonary
Vasodilator Agents
Vasodilation
In Vitro Techniques
Nitric Oxide
Nitric oxide
Rats
Sprague-Dawley
chemistry.chemical_compound
Adenosine Triphosphate
Physiology (medical)
Internal medicine
Potassium Channel Blockers
Medicine
Animals
Nitric Oxide Donors
RNA
Messenger
Hypoxia
Lung
Hypertrophy
Right Ventricular
business.industry
Receptors
Endothelin
Endothelins
Cell Biology
Hypoxia (medical)
medicine.disease
Pulmonary hypertension
Receptor
Endothelin B
Peptide Fragments
Rats
Perfusion
Endocrinology
medicine.anatomical_structure
chemistry
Chronic Disease
medicine.symptom
business
Endothelin receptor
Zdroj: The American journal of physiology. 276(2)
ISSN: 0002-9513
Popis: To investigate whether chronic hypoxia affects endothelin-B (ETB) receptor-mediated pulmonary vasodilation, we compared the vasodilator responses to IRL-1620, a selective ETB-receptor agonist, in isolated perfused lungs from normoxic and chronically hypoxic adult male rats. IRL-1620 caused a dose-dependent vasodilation that was greater in the hypertensive lungs than in the normotensive lungs. In normotensive lungs, a nitric oxide (NO) synthase inhibitor, N ω-nitro-l-arginine (l-NNA; 300 μM), and an ATP-sensitive potassium (KATP)-channel inhibitor, glibenclamide (Glib; 10 μM), each reduced the vasodilator response to IRL-1620 (1 nM), but the combination ofl-NNA and Glib inhibited it more effectively than either drug alone. In contrast,l-NNA alone, but not Glib alone, completely blocked IRL-1620-induced vasodilation in hypertensive lungs. The vasodilator response to a KATP-channel opener, NIP-121 (1 μM), but not the response to sodium nitroprusside (1 μM), was enhanced in hypertensive lungs. We also found increased expression of mRNA for the ETB receptor in lung tissue after hypoxic exposure. In addition, semiquantitative immunohistochemistry demonstrated higher expression levels of ETB receptors in the endothelium of distal segments of the pulmonary artery in hypoxic than in normoxic rats. These results suggest that ETB receptor-mediated pulmonary vasodilation is augmented after chronic hypoxic exposure and that release of NO may be the sole mechanism of this vasodilation in hypertensive lungs, whereas both release of NO and activation of KATP channels are involved in normotensive lungs. We speculate that the underlying mechanism responsible for this augmentation may partly be related to upregulation of ETB receptors in the endothelium of pulmonary resistance arteries in hypertensive lungs.
Databáze: OpenAIRE
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