Studies on production and function of pulmonary nitric oxide

Abstract: Nitric oxide is involved in pulmonary vascular and bronchial regulation and appears to be of paramount importance in the adaptation of the pulmonary circulation at birth. Nitric oxide is present in exhaled gas. The main objective of the present study was to investigate the physiological regulation of pulmonary nitric oxide production, considering factors that are known to be important during pulmonary adaptation at birth, with special reference to the role of nitric oxide in the regulation of pulmonary vascular function. An animal model for continuous analysis of single-breath quantification of lower airway nitric oxide, by chemiluminescence, in vivo was established. The findings show that respiratory system nitric oxide formation is stimulated by stretch-sensitive and [beta]1-adrenoceptor sensitive calcium dependent processes, where the stretch-sensitive process can be blocked by gadolinium. The marked increase in pulmonary vascular resistance upon gadolinium, by far exceeding that attained by direct blockade of NO synthase, suggests that one or several other powerful vasodilators are activated by stretch during pulmonary breathing-induced excursions. The [beta]1-adrenoceptive mechanism is activated by adrenaline released from the adrenals. Carbon dioxide exerts a rapid inhibitory effect on pulmonary nitric oxide formation and especially when nitric oxide formation is stimulated by stretch. It is likely that the findings presented here represent important regulatory mechanisms on pulmonary nitric oxide production, and therefore are of importance for extrauterine pulmonary adaptation at birth and continuous ventilation/perfusion matching throughout extrauterine life.