Pulmonary hypertension is a syndrome of elevated pulmonary arterial pressure, pulmonary vascular resistance, or both. It complicates about 10% of cases of chronic lung diseases, or can have unknown cause (so called primary pulmonary hypertension). It is associated with a significant mortality and morbidity. Factors most important in the pathogenesis of pulmonary hypertension inlude pulmonary vasoconstriction and proliferation of vascular smooth muscle and connective tissue. Currently, there is no reliable and effective therapy available. In a search for one, we tried an inhalation of aerosolized NO-releasing compound, which proved effective.
We hypothesized that when aerosolized solution of an NO-generating substance will be repeatedly inhaled, it will adhere to the walls of the airways for some time, and NO produced during this time will reduce pulmonary hypertension. Indeed, daily inhalations of one such substance, diethylenetriamine NO adduct (DETA/NO), significantly reduced pulmonary hypertension in rats (Figure A). Systemic vasodilation, which complicates and more or less prevents the use of other vasodilators for reducing pulmonary hypertension, did not occurr to any significant degree (Figure B).
Repeated, daily inhalations of aerosolized DETA/NO reduce monocrotaline (MCT)-induced chronic pulmonary hypertension (A) with no significant change in systemic vascular resistance (B).
NS = P>0.05