Chronic hypoxia-induced spontaneous and rhythmic contractions in the rat main pulmonary artery

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 281; no. 1; pp. 183 - L192
• Main Authors: Bonnet, Sebastien, Hyvelin, Jean-Marc, Bonnet, Pierre, Marthan, Roger, Savineau, Jean-Pierre
• Format: Journal Article
• Language: English
• Published: United States 01.07.2001
• Subjects: Animals; Calcium - metabolism; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Chronic Disease; Endothelium, Vascular - physiopathology; Gap Junctions - physiology; Hypertrophy, Right Ventricular - etiology; Hypoxia - complications; Hypoxia - physiopathology; In Vitro Techniques; Male; Membrane Potentials - physiology; Nervous System - physiopathology; Periodicity; Pulmonary Artery - drug effects; Pulmonary Artery - physiopathology; Rats; Rats, Wistar; Time Factors; Vasoconstriction
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.281.1.l183

Laboratoire de Physiologie Cellulaire Respiratoire, Institut National de la Santé et de la Recherche Médicale (Equipe Mixte 9937), and Institut Fédératif de Recherche 4, Université Bordeaux 2, 33076 Bordeaux, France The effect of chronic hypoxia (CH; 1-4 wk) on the electromechanical properties of the rat main pulmonary artery (MPA) was investigated. MPA rings obtained from rats exposed for 14 days to hypobaric (50.5 kPa) CH exhibited spontaneous and rhythmic contractions (SRCs) that were never observed in control (normoxic) rats. SRCs were unaffected by tetrodotoxin, phentolamine, BQ-123 and BQ-788, N -nitro- L -arginine methyl ester, or endothelium removal. CH depolarized smooth muscle cells from 58.8 ± 9 to 38.6 ± 5.4   mV and increased the resting cytosolic Ca 2+ concentration from 67.3 ± 11.9 to 112.5 ± 16.4 nM. CH also induced spontaneous spikelike depolarizations. All of these effects were inhibited by external Ca 2+ removal or nifedipine (1 µM). Moreover, depletion of intracellular Ca 2+ stores with ryanodine (1-5 µM) or cyclopiazonic acid (3 µM) progressively attenuated SRCs. This study demonstrates that CH switches the MPA from a quiescent to a spontaneously active mechanical state. Finally, the fact that SRCs precede the development of right ventricle hypertrophy and disappear when this hypertrophy reaches a maximal value (after 3-4 wk of CH) suggests that SRCs may play a role in the adaptive process of the pulmonary circulation to CH. calcium signaling; hypobaric hypoxia; pulmonary hypertension; smooth muscle; right ventricle hypertrophy