Effect of chronic hypoxia on agonist-induced tone and calcium signaling in rat pulmonary artery.
The effect of chronic hypoxia (CH) for 14 days on Ca2+ 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 Ca2+ concentration ([Ca2+]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 Ca2+ and the sources of Ca2+ implicated in the agonist-induced response were not changed. Analysis of the transient caffeine-induced [Ca2+]i response revealed that recovery of the resting [Ca2+]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 Ca2+ signaling and Ca2+ sensitivity of the contractile apparatus. A Ca2+ reuptake mechanism appears as a CH-sensitive phenomenon that may account for the main effect of CH on Ca2+ signaling.
Bonnet
S
S
Laboratoire de Physiologie Cellulaire Respiratoire, Institut National de la Santé et de la Recherche Médicale (Equipe Mixte 9937), Université Bordeaux 2, 33076 Bordeaux, France.
Belus
A
A
Hyvelin
J M
JM
Roux
E
E
Marthan
R
R
Savineau
J P
JP
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002908:Chronic Disease; D019332:Endothelin-1 / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000150:complications; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000503:physiopathology*
D019332:Endothelin-1; D007211:Indoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D002110:Caffeine; D000255:Adenosine Triphosphate; D002118:Calcium; C000543:cyclopiazonic acid