Our long-term goal is to help clarify how the lungs regulate the peptide hormone composition of systemic arterial blood. In the present project, our goal is to evaluate pulmonary aminopeptidase P in terms of its ability to react with intravascular substrates, in particular with bradykinin. At present, little is known about aminopeptidase P in general and pulmonary aminopeptidase P in particular. Thus, our specific aims are 1) to purify and characterize aminopeptidase P of rat lungs; 2) to prepare monoclonal and polyclonal antibodies against the enzyme and then use the antibodies to clarify the cellular and subcellular sites of aminopeptidase P within the lungs; and 3) to examine the ability of aminopeptidase P of intact rat lungs to process bradykinin and a new synthetic substrate, Arg-Pro-Pro-(3H)benzylamide, presented by central venous blood. By so proceeding, we expect to help clarify an enzymic mechanisms by which the lungs prevent bradykinin from entering systemic arterial blood. The information thus obtained should improve understanding of a previously unrecognized non-ventilatory function of the lungs. In addition to the intrinsic interest of learning how the lungs regulate certain peptide hormone systems, our finding may have clinical implications. The lungs are known to contain another enzyme, angiotensin converting enzyme (ACE; a.k.a. kininase II), capable of inactivating bradykinin. Inhibitors of ACE are now used commonly in the treatment of hypertension and congestive heart failure. By clarifying interactions of pulmonary aminopeptidase P with circulating bradykinin, we amy obtain new insights into how systemic arterial blood concentrations of bradykinin are controlled when ACE is fully inhibited.
