EFFECT OF DEHYDROEPIANDROSTERONE ON HYPOXIC PULMONARY VASOCONSTRICTION - A CA2-ACTIVATED K+-CHANNEL OPENER()

In the present study, we investigated the effects of the naturally occ urring hormone dehydroepiandrosterone (DHEA) on hypoxic pulmonary vaso constriction (HPVC) in isolated ferret lungs and on K+ currents in iso lated and cultured ferret pulmonary arterial smooth muscle cells (FPSM Cs). Severe alveolar hypoxia (3% O-2-5% CO2-92% N-2) caused an initial increase in pulmonary arterial pressure (P-pa) that was followed by a reversal in pulmonary hypertension. Maintaining alveolar hypoxia caus ed a sustained secondary increase in P-pa. Pretreating the lungs with the K+-channel inhibitor tetraethylammonium (TEA) caused a small incre ase in baseline P-pa, potentiated HPVC, and prevented the reversal of HPVC during the sustained alveolar hypoxia. Treating the lungs with DH EA caused a near-complete reversal of HPVC in control lungs and in lun gs that were pretreated with TEA. DHEA also reversed the KCl-induced i ncrease in P-pa. In FPSMCs, DHEA caused an adenosine 3',5'-cyclic mono phosphate-and guanosine 3',5'-cyclic monophosphate-independent increas e in activity of the Ca2+-activated K+ (K-Ca) current. In a cell-attac hed configuration, DHEA caused a mean shift of -22 mV in the voltage-d ependent activation of the K-Ca channel. We conclude that DHEA is a no vel K-Ca-channel opener of the pulmonary vasculature.