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Two aerosolized nitric oxide adducts as selective pulmonary vasodilators for acute pulmonary hypertension
Chen F Lam1, Peter V van Heerden, Kenneth F Ilett
1Department of Pharmacology, University of Western Australia, Crawley, Australia. cflam@cyllene.uwa.edu.au
Study 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 H(2)/thromboxane A(2) receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 micro mol 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.