[Effect of levcromakalim and cromakalim on ATP-sensitive K+ channel of pulmonary arterial smooth muscle cells in pulmonary hypertensive rats].
OBJECTIVE
To investigate the effect of levcromakalim and cromakalim on ATP-sensitive K(+) channel (K(ATP)) and mean pulmonary arterial pressure (mPAP) in rats with chronic hypoxic pulmonary hypertension.


METHODS
Ninety Wistar rats were divided randomly into a normal group (15) and a chronic hypoxia group (75). Rats in the hypoxia group were exposed to hypoxia (FiO(2) = 0.10 +/- 0.05) for 3 weeks, whereas rats in the normal group maintained in air. The currents of K(ATP) of pulmonary artery smooth muscle cells (PASMCs) from both the chronic hypoxic and the normal groups were observed using patch-clamp technique inside-out configuration, and the effect of levcromakalim and cromakalim on K(ATP) from chronic hypoxic group was determined under normoxic conditions. The mPAP and mSAP were determined by catheterization in hypoxic rats before and after levcromakalim and cromakalim were administrated respectively to the rats with doses ranging from 100 micro g/kg to 200 micro g/kg intravenously.


RESULTS
Chronic hypoxia had little effect on the activity of K(ATP) in the chronic hypoxic rats. Levcromakalim and cromakalim remarkably activated the K(ATP) in chronic hypoxic rats. A dose-dependent decreasing effect on mPAP was elicited by levcromakalim and cromakalim in the hypoxic rats.


CONCLUSIONS
Although K(ATP) activity is probably not directly involved in the development of chronic hypoxic pulmonary hypertension in rats, both levcromakalim and cromakalim decrease the increased mPAP induced by chronic hypoxia by activating K(ATP) of SMCs from pulmonary arteries, therefore diminishing the inhibitory effect of hypoxia on other K(+) channels.
Xiao
Xin-rong
XR
Dept. of Respiration, Chengdu Military General Hospital, Chengdu 610083, China.
Cheng
De-yun
DY
Chen
Wen-bin
WB
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects*; D011651:Pulmonary Artery / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D015221:Potassium Channels; D019806:Cromakalim