Monocrotaline injection in rats induced early endothelial injury by day 4, followed by smooth muscle extension by day 8, and increased baseline pulmonary artery pressure by day 12 (P<0.01).
Monocrotaline-induced pulmonary hypertension in rats is preceded by early endothelial injury and followed by increased pulmonary vascular reactivity and smooth muscle extension.
We used awake, unsedated rats with indwelling cardiovascular catheters to study the role of endothelial injury and increased pulmonary vascular reactivity in the pathogenesis of monocrotaline (MC)-induced pulmonary hypertension. Hemodynamic findings were correlated with morphometric analyses of alterations in the vascular endothelium assessed by electron microscopy and of muscularization of pulmonary arteries assessed by light microscopy. Male Sprague-Dawley rats (200-250 g) were injected with MC (60 mg/kg) or with saline vehicle. The hemodynamic response to acute hypoxia (10% O2 for 10 min) was studied at 4, 8, and 12 days postinjection. Pulmonary artery pressures and resistances (Ppa, Rp) were similar in saline- and MC-injected rats at 4 and 8 days postinjection. In response to acute hypoxia, the rise in Ppa was also similar, but there was a slight but significant rise in Rp, (P less than 0.05) in the 8-day group, due largely to a decrease in cardiac output. At 12 days after injection, base-line Ppa was increased in MC-injected rats (P less than 0.01) and there was a heightened response to hypoxia assessed both as a significant increase in Ppa and Rp (P less than 0.05 each). Endothelial injury was observed as early as 4 days postinjection with pallor and swelling evident qualitatively and by a decreased proportion of microfilaments (P less than 0.05) assessed quantitatively. By light microscopy, extension of smooth muscle into normally nonmuscularized pulmonary arteries was evident by 8 days postinjection. By 12 days postinjection there was marked extension of smooth muscle present (P less than 0.01) with medial hypertrophy of muscular arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Rosenberg et al. (Thu,) conducted a other in Monocrotaline-induced pulmonary hypertension. Monocrotaline vs. Saline vehicle was evaluated on Hemodynamic response to acute hypoxia, endothelial injury, and muscularization of pulmonary arteries. Monocrotaline injection in rats induced early endothelial injury by day 4, followed by smooth muscle extension by day 8, and increased baseline pulmonary artery pressure by day 12 (P<0.01).