CELLULAR MECHANISMS OF HYPOXIA-INDUCED CONTRACTION IN HUMAN AND RAT PULMONARY-ARTERIES

The effect of hypoxia was investigated in human (HPA) and rat (RPA) pu lmonary arteries. Hypoxia-induced contraction was 95 +/- 8.7% and 9.3 +/- 4.8% of the control response to K+-rich (80 mM) solution in HPA an d RPA, respectively (n = 10). When RPA strips were precontracted with phorbol 12,13 dibutyrate (0.2 mu M), hypoxia elicited a larger contrac tion (105 +/- 13.4% of the control response, n = 8). In both types of artery, hypoxia-induced contraction was dependent on the extracellular calcium concentration (66 +/- 8.4% and 40 +/- 14.4%, reduction for 1. 25 mM Ca2+ in HPA and RPA, respectively, n = 6) and was inhibited by v erapamil (0.05-10 mu M) and nifedipine (0.05-1 mu M). Glibenclamide (5 -10 mu M) increased the amplitude of hypoxia-induced contraction (+42 +/- 5.3%, n = 5). Hypoxia-induced contraction was blocked by cromakali m (1 mu M) and this effect was reversed by glibenclamide (5 mu M). Thi s contraction was also inhibited by iodoacetic acid (250 mu M). In bet a-escin skinned pulmonary arterial strips, hypoxia had no effect on th e calcium concentration-tension relationship. These results suggest th at the O-2 sensor in the pulmonary artery is located on the vascular s mooth muscle plasmalemma. Hypoxia-induced contraction is dependent on calcium influx through voltage sensitive calcium channels. Its amplitu de is modulated by the functioning of potassium channels.