JTV-506, a new K(ATP) channel opener, relaxes pulmonary artery isolated from monocrotaline-treated pulmonary hypertensive rats.
OBJECTIVE
Vasodilators are considered effective in the treatment of pulmonary hypertension if the vascular reactivity remains reversible. This study was designed to investigate the possibility that JTV-506, a new adenosine trisphoshate-sensitive potassium channel opener, may serve as a useful vasodilator in the treatment of pulmonary hypertension.


METHODS
After approval by the animal care committee, with the use of the isometric-force recording method, the effects of JTV-506 (1 nM-100 micro M) on the contractile response to norepinephrine (0.1 micro M) were examined in pulmonary arteries isolated from monocrotaline (MCT)-treated (i.e., presumed pulmonary hypertensive) and age-matched control rats. The experiments were performed in the presence of endothelium with or without treatment with N(G)-nitro- l-arginine (L-NAME, 100 micro M), and in its absence.


RESULTS
JTV-506 relaxed ( P < 0.05) norepinephrine-preconstricted, endothelium-intact arteries from MCT-treated and control rats. However, the vasorelaxation was greater ( P < 0.05) in the arteries from MCT-treated rats than in controls. L-NAME treatment attenuated ( P < 0.05) vasorelaxation in the arteries from both MCT-treated and control rats. However, endothelial removal attenuated ( P < 0.05) vasorelaxation only in the arteries from MCT-treated rats and not in control arteries.


CONCLUSIONS
JTV-506 may possibly attenuate pulmonary vascular tone through its direct action on vascular smooth muscle cells. In the presence of MCT-induced pulmonary hypertension, JTV-506 may further attenuate pulmonary vascular tone through its direct action on endothelial cells, possibly by stimulating the endothelial release of NO.
Tsutsumi
Yohsuke
Y
Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, 852-8501 Nagasaki, Japan.
Makita
Tetsuji
T
Yamaguchi
Koji
K
Shibata
Osamu
O
Sumikawa
Koji
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D002839:Chromans; C107494:JTV 506; D015221:Potassium Channels; D009569:Nitric Oxide; D016686:Monocrotaline; D000255:Adenosine Triphosphate; D019331:NG-Nitroarginine Methyl Ester