Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension

Inhaled nitric oxide (NO) causes selective pulmonary vasodilation and improves gas exchange in acute lung failure. In experimental pulmonary hypertension, we compared the influence of the aerosolized vasodilatory prostaglandins (PG) PGI(2) and PGE(1) on vascular tone and gas exchange to that of infused prostanoids (PGI(2), PGE(1)) and inhaled NO. An increase of pulmonary artery pressure (P-pa) from 8 to similar to 34 mmHg was provoked by continuous infusion of U-46619 (thromboxane A(2) (TxA(2) analogue) in blood-free perfused rabbit lungs. This was accompanied by formation of moderate lung oedema and severe ventilation-perfusion (V'/Q') mismatch, with predominance of shunt flow (>50%, assessed by the multiple inert gas elimination technique). When standardized to reduce the P-pa by similar to 10 mmHg, inhaled NO (200 ppm), aerosolized PGI(2) (4 ng.kg(-1).min(-1)) and nebulized PGE(1) (8 ng.kg(-1).min(-1)) all reduced both pre- and postcapillary vascular resistance, but did not affect formation of lung oedema. All inhalative agents improved the V'Q' mismatch and reduced shunt flow, the rank order of this capacity being NO > PGI(2) > PGE(1). In contrast, lowering of P-pa by intravascular administration of PGI(2) and PGE(1) did not improve gas exchange. ''Supratherapeutic'' doses of inhaled vasodilators in control lungs (400 ppm NO, 30 ng.kg(-1).min(-1) of PGI(2) or PGE(1)) did not provoke vascular leakage or affect the physiological V'/Q' matching. We conclude that aerosolization of prostaglandins I-2 and E-1 is as effective as inhalation of nitric oxide in relieving pulmonary hypertension. When administered via this route instead of being infused intravascularly, the prostanoids are capable of improving ventilation-perfusion matching, suggesting selective vasodilation in well-ventilated lung areas.