Functional assessment of the pulmonary microcirculation during postnatal development

It has been well documented that the lungs are able to remove or metabolize several vasoactive substances passing through the pulmonary circulation. One such function, the conversion of angiotensin I to angiotensin II and hydrolysis of bradykinin to inactive peptide fragments is performed by angiotensin-converting enzyme (ACE). Although a precise role of these functions for systemic vasoregulation has not been defined, measurement of pulmonary metabolic capacity has the potential for providing substantial information about the integrity and physiology of the pulmonary microcirculation. Studies are described using 3H-benzoyl-phenylalanyl-alanyl-proline (a synthetic substrate for pulmonary ACE) in developing conscious lambs and older sheep. Outflow curves from indicator dilution measurements contain information regarding apparent kinetics of ACE activity. Using a nonlinear model for saturable pulmonary metabolic functions, the derived data demonstrate a) a marked increase in Vmax, the apparent maximal velocity of ACE, with age; and b) no significant change with age in apparent Km, the concentration at which the velocity of ACE is one-half Vmax. This approach has the potential for providing a biochemical tool for examining postnatal growth of the pulmonary microcirculation as well as functional integrity of the pulmonary endothelium during a variety of conditions.