| Objective To investigate the different electrophysiology characteristics of the calcium-activated chloride channels in pulmonary arterial smooth muscle cells between pulmonary arterial hypertension rats induced by left to right shunt and normotensive rats , and to study it's possible role during the progress of pulmonary hypertension induced by high pulmanry blood flow.Methods 40 SD rats(male and female, regardless), aged 6～7 weeks, eighted 180～220g were randomly divided into three groups : group A(control,n=10);group B(sham group ,n=10):only open abdomen and expose abdominal aorta and inferior vena cava; group C( PAH model group, n=20):shunting from abdominal aorta and inferior vena cava to establish pulmonary arterial hypertension. After operation, these rats were raised in the same condition for 11 weeks. Right ventricular systolic pressure (RVSP) of each rat was measured by right cardiac catheterization procedure. Right ventricular hypertrophy index (RVHI) was calculated and expressed as the ratio of right ventricular mass to left ventricular plus septal mass[RV/(LV+S)]. Then the rats were exsanguinated and the intrapulmonary arteries were collected, single PASMC was obtained by acute enzyme separation method (collagenase I and plus papain)and the conventional whole-cell patch clamp technique was used to record resting membrane potential(Em), the Ca2+-activated Cl—channels and the current density, comparing the I-V curve between each group .Results (1)The RVSP and RVHI of group C(PAH model group) were significantly higher than that of group A(control group),group B(sham group),(P<0.01); The difference of the RVSP and RVHI between group A and group B was not significant(P>0.05).(2)The Em of group C [(-36.837±2.809)mV]was significantly higher than that of group A[(-48.574±2.558)mV], (P<0.01); The Em of group B was [(-49.218±1.855)mV],comparing with group A, The difference was not significant,(P>0.05) .(3)The peak current density at +80 mV of outward Calcium-activated chloride channel current(Itd) : In group A [(37.864±59.06) pA],and group B[(35.177±3.768) pA],group C [(35.248±3.003) pA], the difference were not statistically significant among these three groups (P>0.01) . The peak current density at +20 mV of inward Calcium-activated chloride channel currents: In group C [(-58.94±11.14)pA/pF],it's absolute value was significantly higher than that of group A [(-47.59±5.16) pA/pF] and group B[(-41.363±1.75) pA/pF] (P<0.01, respectively); The difference between group B and group A was not significant,P>0.05 . (5)There was no significant drift about the I-V curve of Itd PASMCs . (6)compared with group A and group B, the I-V curve about Itail of group C was significantly downward shift; the difference between group A and group B was not significant . (7)There was a positive correlation between Em and RVSP(P<0.01), and a negative correlation between Itail and RVSP(P<0.01). There was no correlation between Itd and RVSP, also no correlation beweent Itd and Em.Conclusions (1)During the formation process of left-to-right shunt induced pulmonary arterial hypertension, with the stepping up of pulmonary arterial pressure, the Em of PASMCs stepping up. (2)The absolute value of current density of inward calcium-activated chloride channel currents was increased, and it's I-V curve was shift downward. (3)These suggested that the change of Calcium-activated chloride ion channel currents may play a role in the pulmonary arterial hypertension induced by left-to-right shunting. |
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