Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats

This paper reports the effect of triptolide (a diterpenoid triepoxide) on t he development of monocrotaline (MCT)-induced pulmonary hypertension in pne umonectomized 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 mi of ethanol/cremophor intraperitoneally, every other day , n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmo nary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 vers us 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significant ly less right ventricular hypertrophy (RVH) and pulmonary arterial neointim al 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), grea ter 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, triptolid e attenuates the development of pulmonary hypertension and RVH, and promote s regression of pulmonary arterial neointimal formation.