Contribution of chloride channel activation to the elevated muscular tone of the pulmonary artery in monocrotaline-induced pulmonary hypertensive rats.
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.
Nakazawa
H
H
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
Hori
M
M
Murata
T
T
Ozaki
H
H
Karaki
H
H
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D017931:DNA Primers; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage*; D009129:Muscle Tonus / Q000502:physiology*; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000494:pharmacology
D018118:Chloride Channels; D017931:DNA Primers; D016686:Monocrotaline; D014700:Verapamil; D002118:Calcium