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

Abstract

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.

Angiotensin-Converting Enzyme Inhibitor Preserves p21 and Endothelial Nitric Oxide Synthase Expression in Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

“…33,34 Although the pathogenesis and pathophysiology of this model cannot be considered identical to all forms of human PAH, the MCT-induced PAH model shows endothelial injury and dysfunction, which is generally seen in human PAH. 35 We still need to investigate, however, whether our findings in this model can be reproducible in other PAH models.…”

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

“…MCT-induced pulmonary hypertension is a well-known experimental model of pulmonary vascular disease that has an important inflammatory component [19]. MCT causes endothelial injury and subsequent endothelial dysfunction of pulmonary arteries [20]. Impaired endothelium-dependent relaxation is caused by endothelial dysfunction and/or reduced vasodilator function in vascular smooth muscle.…”

Time-Dependent Phenotypic and Contractile Changes of Pulmonary Artery in Chronic Hypoxia–Induced Pulmonary Hypertension

“…For example, PASMCs are continuously depolarized and accordingly cytosolic Ca 2+ levels increase (41). Ito et al found that increments of the basal active tonus of pulmonary artery in monocrotaline-induced pulmonary hypertensive rat are associated with membrane depolarization (42,43). Although the depolarization mechanism is not fully understood, Cl − -channel activation can partly explain it (24,44).…”