Alterations of endothelium and smooth muscle function in monocrotaline-induced pulmonary hypertensive arteries

• Published in: American journal of physiology. Heart and circulatory physiology 2000-10, Vol.279 (4), p.H1786-H1795
• Main Authors: Ito, Kaoru M, Sato, Miharu, Ushijima, Keiko, Nakai, Masaaki, Ito, Katsuaki
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Culture Media - metabolism; Culture Media - pharmacology; Endothelium, Vascular - physiopathology; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - physiopathology; Intracellular Membranes - metabolism; Male; Membrane Potentials; Monocrotaline; Muscle, Smooth, Vascular - physiopathology; Nitric Oxide - physiology; Osmolar Concentration; Pulmonary Artery - physiopathology; Rats; Rats, Wistar; Vasodilator Agents - pharmacology; Vasomotor System - physiopathology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2000.279.4.h1786

Departments of 1  Veterinary Pharmacology and 2  Anatomy, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2192, Japan 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 -nitro- L -arginine (200 µM), 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. nitric oxide; membrane potential; depolarization; sodium nitroprusside; resting tone