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

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Title: Phosphodiesterase V Inhibitors Dilate the Pulmonary Artery of Monocrotaline-Induced Pulmonary Hypertensive Rats
Authors: Makita, Tetsuji / Tsutsumi, Yohsuke / Cho, Sungsam / Shibata, Osamu / Sumikawa, Koji
Issue Date: Mar-2005
Citation: Acta medica Nagasakiensia. 2005, 50(1), p.29-33
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 μmM), 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 saline- or monocrotaline- treated rats. There was no difference in the dilatory effect between monocrotaline and saline rats. Pretreatment of a NOS inhibitor (NG-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.
Keywords: PDEVinhibitor / Monocrotaline / Rat / Pulmonaryhypertension
URI: http://hdl.handle.net/10069/9325
ISSN: 00016055
Relational Links: http://joi.jlc.jst.go.jp/JST.JSTAGE/amn/50.29
Type: Departmental Bulletin Paper
Text Version: publisher
Appears in Collections:Volume 50, No. 1

Citable URI : http://hdl.handle.net/10069/9325

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