Objective: To investigate the effects of long-term application of L-arginine (L-Arg) on K(+) channel in pulmonary artery smooth muscle cells (PASMC) from rats exposed to chronic hypoxia.
Methods: Male Wistar rats were randomly divided into three groups: group A (control group), group B (chronic hypoxia group) and group C (chronic hypoxia plus L-Arg treatment group). The rats were exsanguinated and the intrapulmonary arteries (300 approximately 700 OD) were collected. Single PASMC was obtained by the acute enzyme separation method (collagnase Iplus papain) and the conventional whole-cell patch clamp technique was used to record resting membrane potential (Em), potassium ion currents of voltage-gated potassium channel and Ca(2+)-sensitive potassium channel.
Results: (1) The Em of group B [(-31 +/- 8) mV, n = 6] was significantly higher than that of group A [(-42 +/- 5) mV, n = 6, P < 0.01]. After long-term application of L-Arg, the Em of group C [(-39 +/- 4) mV, n = 6] was significantly lower than that of group B (P < 0.05). (2) The peak current at +50 mV of voltage-gated potassium channel was compared among three groups. In group B [(62.2 +/- 5.3) pA/pF, n = 6], it was significantly lower than that of group A [(121 +/- 9) pA/pF, n = 6] (P < 0.01). After long-term application of L-Arg, the peak current at +50 mV of voltage-gated potassium channel in group C [(95 +/- 3) pA/pF, n = 6] was significantly higher than that of group B (P < 0.001). (3) The peak current at +50 mV of Ca(2+)-sensitive potassium channel was compared among three groups. In group B [(74.7 +/- 4.1) pA/pF, n = 6], it was significantly higher than that of group A [(53.6 +/- 5.9) pA/pF, n = 6] (P < 0.05). After long-term application of L-Arg, the peak current at +50 mV of Ca(2+)-sensitive potassium channel in group C [(31.8 +/- 1.8) pA/pF, n = 6] was significantly lower than that of group B [(74.7 +/- 4.1) pA/pF, n = 6] (P < 0.001).
Conclusions: The long-term application of L-Arg can improve the resting membrane potential of PASMCs from rats exposed to chronic hypoxia, increase the currents of voltage-gated potassium channel and decrease the currents of Ca(2+)-sensitive potassium channel. These effects are considered to be effective in improving chronic hypoxic pulmonary hypertension.