Effect of dehydroepiandrosterone on hypoxic pulmonary vasoconstriction: a Ca21-activated K1-channel opener

Farrukh, Imad S., Wei Peng, Urszula Orlinska, and John R. Hoidal. Effect of dehydroepiandrosterone on hypoxic pulmonary vasoconstriction: a Ca21-activated K1channel opener. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L186–L195, 1998.—In the present study, we investigated the effects of the naturally occurring hormone dehydroepiandrosterone (DHEA) on hypoxic pulmonary vasoconstriction (HPVC) in isolated ferret lungs and on K1 currents in isolated and cultured ferret pulmonary arterial smooth muscle cells (FPSMCs). Severe alveolar hypoxia (3% O2-5% CO2-92% N2) caused an initial increase in pulmonary arterial pressure (Ppa) that was followed by a reversal in pulmonary hypertension. Maintaining alveolar hypoxia caused a sustained secondary increase in Ppa. Pretreating the lungs with the K1channel inhibitor tetraethylammonium (TEA) caused a small increase in baseline Ppa, potentiated HPVC, and prevented the reversal of HPVC during the sustained alveolar hypoxia. Treating the lungs with DHEA caused a near-complete reversal of HPVC in control lungs and in lungs that were pretreated with TEA. DHEA also reversed the KCl-induced increase in Ppa. In FPSMCs, DHEA caused an adenosine 38,58-cyclic monophosphateand guanosine 38,58-cyclic monophosphate-independent increase in activity of the Ca21activated K1 (KCa) current. In a cell-attached configuration, DHEA caused a mean shift of 222 mV in the voltagedependent activation of the KCa channel. We conclude that DHEA is a novel KCa-channel opener of the pulmonary vasculature.