Contribution of Chloride Channel Activation to the Elevated Muscular Tone of the Pulmonary Artery in Monocrotaline-Induced Pulmonary Hypertensive Rats

The Japanese Journal of Pharmacology

Hideaki Karaki¹  Hiroshi Ozaki¹  Masatoshi Hori¹  Takahisa Murata¹  Hiroshi Nakazawa¹ 

[1] Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo

关键词: Cl− channel;    Pulmonary hypertension;    Smooth muscle;    Vasoconstriction;    Monocrotaline;   

DOI  :  10.1254/jjp.86.310

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)Cited-By(13)In monocrotaline-treated rat pulmonary artery from which endothelium was removed, greater spontaneous muscular tone was observed under resting conditions than in vehicle-treated artery. The aim of the present study was to show the possible contribution of Cl− channels in the mechanism of the elevated tone. Verapamil almost completely inhibited the elevated spontaneous muscular tone by decreasing [Ca2+]i. The elevated muscular tone was also inhibited by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), a Cl− channel inhibitor. After the inhibition of muscular tone by DIDS, verapamil did not induce further relaxation. Quantitative RT-PCR analysis indicated that the mRNA levels of ClC3 and Ca2+-activated Cl− channels did not change in the pulmonary hypertensive pulmonary artery from those of vehicle-treated rats. These results suggest that the elevated muscular tone observed in the monocrotaline-induced hypertensive pulmonary artery is due to membrane depolarization of smooth muscle cells and that this phenomenon might be mediated by the activation of DIDS-sensitive Cl− channels.

【 授权许可】

Unknown