[The effects of long-term application of L-arginine on K+ channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia].
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.
Zhang
Yong-chang
YC
Respiratory Department of Tongji Hospital, Tongji Medical School of Huazhong University of Science and Technology, Wuhan 430030, China.
Ni
Wang
W
Zhen
Guo-hua
GH
Zhang
Zhen-xiang
ZX
Xu
Yong-jian
YJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011651:Pulmonary Artery / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D001120:Arginine