Two aerosolized nitric oxide adducts as selective pulmonary vasodilators for acute pulmonary hypertension.
OBJECTIVE
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.


CONCLUSIONS
Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.
Lam
Chen F
CF
Department of Pharmacology, University of Western Australia, Crawley, Australia. cflam@cyllene.uwa.edu.au
van Heerden
Peter V
PV
Ilett
Kenneth F
KF
Caterina
Paul
P
Filion
Pierre
P
D000336:Aerosols; D000475:Alkenes / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D009603:Nitroso Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000336:Aerosols; D000475:Alkenes; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D014665:Vasodilator Agents; C453079:dipropylenetriamine-NONOate; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine