Effect of chronic hypoxia on agonist-induced tone and calcium signaling in rat pulmonary artery

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 281; no. 1; pp. 193 - L201
• Main Authors: Bonnet, Sebastien, Belus, Alexandra, Hyvelin, Jean-Marc, Roux, Etienne, Marthan, Roger, Savineau, Jean-Pierre
• Format: Journal Article
• Language: English
• Published: United States 01.07.2001
• Subjects: Adenosine Triphosphate - pharmacology; Angiotensin II - pharmacology; Animals; Caffeine - pharmacology; Calcium - metabolism; Calcium Signaling; Chronic Disease; Endothelin-1 - pharmacology; Hypertension, Pulmonary - complications; Hypertrophy, Right Ventricular - etiology; Hypoxia - complications; Hypoxia - physiopathology; In Vitro Techniques; Indoles - pharmacology; Intracellular Membranes - metabolism; Male; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Pulmonary Artery - drug effects; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Rats; Rats, Wistar; Reference Values; Vasoconstriction; Vasodilator Agents - pharmacology; Vasomotor System - physiopathology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.281.1.l193

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) for 14 days on Ca 2+ signaling and contraction induced by agonists in the rat main pulmonary artery (MPA) was investigated. In MPA myocytes obtained from control (normoxic) rats, endothelin (ET)-1, angiotensin II (ANG II), and ATP induced oscillations in intracellular Ca 2+ concentration ([Ca 2+ ] i ) in 85-90% of cells, whereas they disappeared in myocytes from chronically hypoxic rats together with a decrease in the percentage of responding cells. However, both the amount of mobilized Ca 2+ and the sources of Ca 2+ implicated in the agonist-induced response were not changed. Analysis of the transient caffeine-induced [Ca 2+ ] i response revealed that recovery of the resting [Ca 2+ ] i value was delayed in myocytes from chronically hypoxic rats. The maximal contraction induced by ET-1 or ANG II in MPA rings from chronically hypoxic rats was decreased by 30% compared with control values. Moreover, the D-600- and thapsigargin-resistant component of contraction was decreased by 40% in chronically hypoxic rats. These data indicate that CH alters pulmonary arterial reactivity as a consequence of an effect on both Ca 2+ signaling and Ca 2+ sensitivity of the contractile apparatus. A Ca 2+ reuptake mechanism appears as a CH-sensitive phenomenon that may account for the main effect of CH on Ca 2+ signaling. angiotensin II; endothelin-1; calcium oscillations; vascular smooth muscle; pulmonary hypertension