Phosphodiesterase V Inhibitors Dilate the Pulmonary Artery of Monocrotaline-Induced Pulmonary Hypertensive Rats

Accession number;05A0587719
Title;Phosphodiesterase V Inhibitors Dilate the Pulmonary Artery of Monocrotaline-Induced Pulmonary Hypertensive Rats
Author; MAKITA TETSUJI (Nagasaki Univ. Hospital, Nagasaki, Jpn) TSUISUMI YOHSUKE (Nagasaki Univ. Graduate School Of Biomedical Sci., Nagasaki, Jpn) CHO SUNGSAM (Nagasaki Univ. Hospital, Nagasaki, Jpn) SNIBATA OSAMU (Nagasaki Univ. Graduate School Of Biomedical Sci., Nagasaki, Jpn) SUMIKAWAZ KOJI (Nagasaki Univ. Graduate School Of Biomedical Sci., Nagasaki, Jpn)
Journal Title;Acta Med Nagasaki Ensia
Journal Code:X0952A
ISSN:0001-6055
VOL.50;NO.1;PAGE.29-33(2005)
Figure&Table&Reference;FIG.3, REF.22
Pub. Country;Japan
Language;English
Abstract;Treatment of pulmonary hypertension has not yet been established and effective drug therapies are required. We hypothesized that inhibition of cyclic guanosine monophoshate (cGMP)- phosphodiesterase (PDE) would result in specific vasodilation of the hypertensive pulmonary arteries. This study was carried out to determine whether PDE V inhibitors could dilate pulmonary artery (PA) from monocrotaline-induced pulmonary hypertensive rats. Thirty-six Wistar rats were given either monocrotaline (105 mg/kg) or normal saline (control) subcutaneously. Three weeks later, the PA rings were isolated and mounted in 5-mL organ chambers. After precontraction with norepinephrine (0.1 umM), one of two PDE V inhibitors, zaprinast and dipyridamole, was added in a cumulative fashion. We also investigated whether nitric oxide synthetase (NOS) inhibitor modifies the effects of the PDE V inhibitors on the PA. Zaprinast and dipyridamole dose-dependently dilated the PA from either salineor monocrotaline-treated rats. There was no difference in the dilatory effect between monocrotaline and saline rats. Pretreatment of a NOS in- hibitor (N'G'-nitro-L-arginine methyl ester (0.1 mM)) reduced moderately the vasodilatory effect of zaprinast on the PA from monocrotaline-treated but not saline-treated rats. The results suggest that PDE V inhibitors exert a strong vasodilating effect on PA of pulmonary hypertensive rats as well as on that of normal rats, and that NO plays a role, at least in part, in the effect of PDE V inhibition on PA of pulmonary hypertensive rats. (author abst.)
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