Endothelial injury and vascular reactivity in monocrotaline XXXX .

@entity35 @entity519 @entity358 @entity120
We used awake, unsedated @entity35 with indwelling cardiovascular catheters to study the role of endothelial injury and @entity358 in the pathogenesis of monocrotaline (MC)-induced @entity120 . 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 @entity35 (200-250 g) were injected with MC (60 mg/kg) or with saline vehicle. The hemodynamic response to acute @entity519 (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 @entity35 at 4 and 8 days postinjection. In response to acute @entity519 , 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 @entity35 (P less than 0.01) and there was a heightened response to @entity519 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)
