The Effect Of K_ca On HPV Attenuated By Chronic Intermittent Hypoxia In RPASMCs

To determine the ionic mechanisms of the hypoxic acclimatization at the level of channels, male Spradue-Dawley rats were divided into two groups: control normoxic group and chronic intermittent hypoxic group (O2 concentration: 10±0.5 %, hypoxia 8 hours a day). Using whole cell patch-clamp technique, calcium-actived potassium channel currents (IKca) were recorded in freshly isolated pulmonary arterial smooth muscle cells (PASMCs) of rat with acutely isolated method. The effect of acute hypoxia on IKca of PASMCs from chronic intermittent hypoxia group was investigated to offer some basic data for clarifying the ionic mechanisms of the hypoxic acclimatization. The results showed: (1) In control normoxic group, after acute hypoxia the IKca of PASMCs was increased significantly from 48.7±2.4 pA/pF to 66.5±3.4 pA/pF, percentage increase in the peak current was up to 38.4±0.8% at +60 mV, and current-voltage relationship curve shifted to the left. (2) In chronic intermittent hypoxic group, the IKca of PASMCs was increased significantly by exposure to intermittent hypoxia in a time dependent manner, IKca increase appeared to start at day 10 and continued to th day 30 (the longest time tested) of hypoxia (3) Compared with the control normoxic group, the percentage increase in IKca by acute hypoxia was significantly attenuated in the chronic intermittent hypoxia group and this increase effect declined with time exposed to hypoxia. The results suggest that the negative feedback modulatiom effect of Kca was significantly increased by acute and chronic intermittent hypoxia and attenuated significantly in HPV induced by acute hypoxia during chronic intermittent hypoxia group. This may be one of the important mechanisms involved in the development of hypoxic pulmonary vasoconstriction(HPV) and hypoxic pulmonary hypertension(HPH).