Chronic hypoxia alters effects of endothelin and angiotensin on K+ currents in pulmonary arterial myocytes

We tested the hypothesis that chronic hypoxia alters the regulation of K+ c hannels in intrapulmonary arterial smooth muscle cells (PASMCs). Charybdoto xin-insensitive, 4-aminopyridine-sensitive voltage-gated K+ (K-V,K-CI) and Ca2+-activated K+ (K-Ca) currents were measured in freshly isolated PASMCs from rats exposed to 21 or 10% O-2 for 17-21 days. In chronically hypoxic P ASMCs, K-V,K-CI current was reduced and K-Ca current was enhanced. 4-Aminop yridine (10 mM) depolarized both normoxic and chronically hypoxic PASMCs, w hereas charybdotoxin (100 nM) had no effect in either group. The inhibitory effect of endothelin (ET)-1 (10(-7) M) on K-V,K-CI current was significant ly reduced in PASMCs from chronically hypoxic rats, whereas inhibition by a ngiotensin (ANG) II (10(-7) M) was enhanced. Neither ET-I nor ANG II altere d K-Ca current in normoxic PASMCs; however, both stimulated K-Ca current at positive potentials in chronically hypoxic PASMCs. These results suggest t hat although modulation of K-V,K-CI and K-Ca channels by ET-1 and ANG II is altered by chronic hypoxia, the role of these channels in the regulation o f resting membrane potential was not changed.