Inhaled Nitric Oxide Reverses Vascular and Respiratory Effects of ET-1 and PAF in Pigs

In anaesthetized paralysed, mechanically ventilated pigs, the vascular and respiratory effects of 80 ppm nitric oxide (NO) inhaled for 6 min were evaluated. To evoke different levels of smooth muscle contraction ET-1 or PAF, mediators involved in pulmonary disorders, were used. In control conditions, inhaled NO caused selective pulmonary vasodilatation without affecting respiratory resistances. This pulmonary vascular activity influenced the distensibility of the respiratory system and decreased inspiratory work. ET-1 administration significantly increased pulmonary arterial pressure and modestly changed mechanical properties of the respiratory system, while PAF caused potent vasoconstriction and bronchoconstriction associated with a marked change in volume-pressure relationship. In both cases, the changes in vascular and mechanical properties of the respiratory system increased inspiratory work. The vascular and respiratory activities of inhaled NO were correlated with preconstriction levels. The data show that the combination of vascular and respiratory effects improves pulmonary function, suggesting that inhalation of NO is a possible therapeutic approach for obstructive and inflammatory pulmonary diseases.