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.