Jpn. J. Pharmacol. 86 (3), 310-315 (2001)

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

Hiroshi Nakazawa, Masatoshi Hori, Takahisa Murata, Hiroshi Ozaki* and Hideaki Karaki

Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan

*Corresponding author. FAX: +81-3-5841-8183, E-mail:

Abstract: 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.

Keywords: Cl channel, Pulmonary hypertension, Smooth muscle, Vasoconstriction, Monocrotaline
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