Metabolic functions of the lung and systemic vasoregulation

Several important vasoactive substances are taken up and/or metabolized during a single transpulmonary passage. Such substances include 5-hydroxytryptamine, prostaglandins (PGs) of the E and F series, and peptide substrates (angiotensin I and bradykinin) for angiotensin-converting enzyme (ACE). When these metabolic processes are altered, predictable changes in systemic hemodynamics can follow because of altered arterial concentrations of the vasoactive substances. For example, a single dose of captopril (2 mg/kg, i.v.) given to conscious rabbits caused prolonged depression in pulmonary ACE activity, an effect that coincided with a significant reduction in mean systemic arterial pressure. In another study, total cardiopulmonary bypass in anesthetized dogs was associated with a time-dependent increase in arterial levels of immunoreactive PGE. Coincident with this elevation in PGE was a significant decrease in total systemic vascular resistance. The decrease in resistance was inhibited by pretreatment with indomethacin or by maintaining lung perfusion during extracorporeal circulation (i.e., left heart bypass). Thus, in the intact animal, significant reduction in lung metabolism, induced by either pharmacological or other experimental means, may modify vasoregulation of peripheral circulation. Furthermore, measurement of these metabolic functions may provide biochemical information about the pulmonary microcirculation, which is both the locus of these activities and an early site of acute lung injury.