Am. J. Respir. Crit. Care Med., Volume 162, Number 6, December 2000, 2252-2258

Triptolide Attenuates Pulmonary Arterial Hypertension and Neointimal Formation in Rats

JOHN L. FAUL, TOSHIHIKO NISHIMURA, GERALD J. BERRY, GAIL V. BENSON, RONALD G. PEARL, and PETER N. KAO

The Division of Pulmonary and Critical Care Medicine, and the Departments of Pathology and Anesthesiology, Stanford University Medical Center, Stanford, California

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.

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