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40-O-(2-hydroxyethyl)-rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats.

Authors :
Nishimura T
Faul JL
Berry GJ
Veve I
Pearl RG
Kao PN
Source :
American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2001 Feb; Vol. 163 (2), pp. 498-502.
Publication Year :
2001

Abstract

Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR(5-35) from Day 5 to Day 35, Group PMR5-14 from Day 5 to Day 14, and Group PMR15-35 from Day 15 to Day 35. By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (Ppa = 41 +/- 3 mm Hg) (p < 0.001), right ventricular systolic pressures (Prv,s = 45 +/- 2 mm Hg) (p < 0.01), and right ventricle/(left ventricle plus septum) (0.55 +/- 0.05) (p = 0.028) than rats in Groups PMR5-35 (Ppa = 25 +/- 3 mm Hg, Prv,s = 32 +/- 7 mm Hg, RV/LV&S = 0.42 +/- 0.06) and PMR5-14 (Ppa = 29 +/- 4 mm Hg, Prv,s = 30 +/- 5 mm Hg, RV/LV&S = 0.43 +/- 0.07). Pulmonary arterial neointimal formation (quantified by a vascular occlusion score) was more severe in vehicle-treated rats (1.93 +/- 0.03) than in Groups PMR5-14 (1.56 +/- 0.27) and PMR(5-35) (1.57 +/- 0.1) (p < 0.01). RAD attenuates the development of MCT-induced pulmonary arterial hypertension in the pneumonectomized rat.

Details

Language :
English
ISSN :
1073-449X
Volume :
163
Issue :
2
Database :
MEDLINE
Journal :
American journal of respiratory and critical care medicine
Publication Type :
Academic Journal
Accession number :
11179130
Full Text :
https://doi.org/10.1164/ajrccm.163.2.2006093