Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats.
This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.
Faul
J L
JL
The Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California 94305-5236, USA.
Nishimura
T
T
Berry
G J
GJ
Benson
G V
GV
Pearl
R G
RG
Kao
P N
PN
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D016686:Monocrotaline; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010616:Phenanthrenes; D011013:Pneumonectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide; D016686:Monocrotaline