Alterations of endothelium and smooth muscle function in monocrotaline-induced pulmonary hypertensive arteries.
We examined how monocrotaline (MCT), which impairs the endothelium and causes pulmonary hypertension, altered the endothelial regulation of pulmonary artery functions. Rats were given a single injection of MCT (60 mg/kg sc). Pulmonary arteries were depolarized to -48.3 +/- 2.6 and -39.8 +/- 2.2 mV at 2 and 3 wk after treatment with MCT, respectively (control arteries -59.9 +/- 1.9 mV). The basal tone in the resting state was only slightly elevated at 3 wk in endothelium-intact arteries. Removal of the endothelium caused further depolarization in MCT-affected arteries at 2 wk, but not at 3 wk, and greatly elevated the basal tone at 2 and 3 wk. N(omega)-nitro-L-arginine (200 microM), a nitric oxide synthase inhibitor, also caused depolarization in endothelium-intact arteries in both groups and elevated the basal tone of MCT-affected arteries. The relaxant responses of pulmonary arteries to ACh and A-23187 were depressed at 2 and 3 wk after MCT treatment. Thus chronic impairment of the endothelium altered the property of the pulmonary artery leading to depolarization. During the early stage of depolarization, a rise in the basal tone was offset by nitric oxide released from the injured endothelium.
Ito
K M
KM
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2192, Japan. ito@grc.miyazaki-u.ac.jp
Sato
M
M
Ushijima
K
K
Nakai
M
M
Ito
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D016686:Monocrotaline; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000503:physiopathology
D003470:Culture Media; D014665:Vasodilator Agents; D009569:Nitric Oxide; D016686:Monocrotaline; D002118:Calcium