objectives: To determine the selective vasodilatory effects of two inhaled “NONOate” aerosols in a closed chest pig model of acute pulmonary hypertension (APH).Methods: APH was induced by IV infusion of the prostaglandin H2/thromboxane A2 receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 μmol each], or placebo (n = 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy.Results: Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p <0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p <0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO.Conclusion: Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.