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: aozaki@mail.ecc.u-tokyo.ac.jp
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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