[Effect of dehydroepiandrosterone on Ca(2+)-activated K+ channel of pulmonary arterial smooth muscle cells in pulmonary hypertensive rats].
OBJECTIVE
To investigate the effects of dehydroepiandrosterone (DHEA) on Ca(2+)-activated K(+) (K(Ca)) channel and mean pulmonary arterial pressure (mPAP) in rats with chronic pulmonary hypertension.


METHODS
Fifty Wistar rats were divided randomly into a normal group (group A, n = 10) and a chronic hypoxia group (group B, n = 40). The rats in group B were subdivided into group B(1), B(2), B(3), and B(4) (each n = 10) at random. The rats in group B were exposed to hypoxia (FiO(2) = 0.10 +/- 0.05) for 3 weeks, whereas the rats in group A maintained in air. Under normoxic conditions, the smooth muscle cells (SMCs) were isolated from the pulmonary artery by the acute enzymatic dissection methods. In the symmetrical high K(+) solution, the K(Ca) currents were separated with inside-out configuration using the patch clamp technique. The activity of K(Ca) currents in SMCs between group B(1) and group A was compared under normoxic conditions, and the effect of DHEA on K(Ca) channel from group B(1) was observed. The mPAP and mean systemic arterial pressure (mSAP) were determined by right cardiac catheterization in rats from group B(2), B(3), B(4) before and after DHEA was administrated to rats by intravenous injection.


RESULTS
The activity of K(Ca) channel in group B rats was much lower than that in group A (P < 0.01). DHEA could reverse the reduced K(Ca) channel in group B(1) rats. The mPAP were decreased significantly (P < 0.01) after DHEA was administrated to the rats in group B(2), B(3), B(4) with little change on mSAP (P < 0.05).


CONCLUSIONS
Persistent decrease of K(Ca) channel activity may take part in the development of chronic hypoxic pulmonary hypertension in rats. DHEA can decrease the increased mPAP induced by chronic hypoxia via activating K(Ca) channel of SMCs from pulmonary arteries.
Department of Respiratory Medicine, Chengdu Army General Hospital, Chengdu 610083, China.
Xin-rong
XR
Xiao
Wen-bin
WB
Chen
De-yun
DY
Cheng
Zhang
Z
Chen
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000276:Adjuvants, Immunologic; D024681:Potassium Channels, Calcium-Activated; D003687:Dehydroepiandrosterone