Nifedipine inhibits pulmonary hypertension but does not prevent decreased lung eNOS in hypoxic newborn pigs

Therapies to prevent the onset or progression of pulmonary hypertension in newborns have received little study compared with those in adult models. We wanted to determine whether nifedipine treatment prevents the increased pu lmonary vascular resistance, blunted pulmonary vascular responses to acetyl choline, and reduced lung endothelial nitric oxide synthase (eNOS) amounts that we have found in a newborn model of chronic hypoxia-induced pulmonary hypertension. Studies were performed with 1- to 3-day-old piglets raised in room air (contral) or 10% O-2 (hypoxia) for 10-12 days. Some piglets from each group were given nifedipine (3-5 mg/kg sublingually three times a day) . Pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured in anesthetized animals. Pulmonary vascular responses to ace tylcholine and eNOS amounts were assessed in excised lungs. The calculated value of the pulmonary vascular resistance for nifedipine-treated hypoxic p iglets (0.09 +/- 0.01 cmH(2)O.ml(-1).min.kg) was almost one-half of the val ue for untreated hypoxic piglets (0.16 +/- 0.01 cmH(2)O.ml(-1).min.kg) and did not differ from the value for untreated control piglets (0.05 +/- 0.01 cmH(2)O.ml(-1).min.kg). Pulmonary arterial pressure responses to acetylchol ine and whole lung homogenate eNOS amounts were less for both nifedipine-tr eated and untreated hypoxic piglets than for untreated control piglets. Nif edipine treatment attenuated pulmonary hypertension in chronically hypoxic newborn piglets despite the persistence of blunted responses to acetylcholi ne and reduced lung eNOS amounts.