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

The effect of chronic hypoxia (CH) for 14 days on Ca2+ signaling and contra ction induced by agonists in the rat. main pulmonary artery (MPA) was inves tigated. In MPA myocytes obtained from control (normoxic) rats, endothelin (ET)-1, angiotensin II (ANG II), and ATP induced oscillations in intracellu lar Ca2+ concentration ([Ca2+](i)) in 85-90% of cells, whereas they disappe ared in myocytes from chronically hypoxic rats together with a decrease in the percentage of responding cells. However, both the amount of mobilized C a2+ and the sources of Ca2+ implicated in the agonist-induced response were not changed. Analysis of the transient. caffeine-induced [Ca2+](i) respons e revealed that recovery of the resting [Ca2+](i) value was delayed in myoc ytes 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-resista nt component. of contraction was decreased by 40% in chronically hypoxic ra ts. These data indicate that CII 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.