Altered expression of ETB-receptor mRNA in the lung of rats with pulmonary hypertension.
To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg), rats (PH rats, n = 6) were sacrificed. Vehicle-injected rats (n = 6) served as controls. The right ventricular systolic pressure of PH rats [58.0 +/- 4.7 mm Hg (mean +/- SEM)] was significantly higher than that in the vehicle-treated control rats (29.2 +/- 2.1; p < 0.01). Northern blot analysis showed that the expression of ETB-receptor mRNA decreased in the lung of PH rats. The venous plasma concentration of ET-1 measured by a sandwich-enzyme immunoassay was significantly higher in PH rats than in control rats (5.1 +/- 0.7 versus 1.3 +/- 0.2 pg/ml; p < 0.01). The present findings suggest that the expression of ETB-receptor mRNA decreases in the lung of PH rats, which might be closely related to the increase in plasma ET-1 concentration in these rats.
Yorikane
R
R
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Miyauchi
T
T
Sakai
S
S
Sakurai
T
T
Yamaguchi
I
I
Sugishita
Y
Y
Goto
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D016232:Endothelins / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000096:biosynthesis*
D016232:Endothelins; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D016686:Monocrotaline