Processing of Endogenous Polypeptides by the Lungs

The lungs in effect clear a number of hormones and prohormones such that their concentrations in systemic arterial blood are significantly altered in comparison with those of the same substances in central venous blood (28, 70-72, 94). The clearance of a given hormone or prohormone may greatly exceed the quantity likely to be needed to support lung function. In some instances, neither the hormone nor prohormone is retained by the lungs but is metabolized such that the reaction products are released into the pulmo­ nary venous effluent and therefore into the systemic arterial circulation (60, 66, 67, 8 1). Through such clearance or processing of hormones, especially polypeptide hormones, the lungs can be said to regulate the hormonal composition of arterial blood (70, 7 1, 74, 75). Little is known about which polypeptide hormones and prohormones are altered during passage through the pulmonary vascular bed and which are not (28, 72). Our knowledge is limited by techniques of assay and by the availability of polypeptides labelled intrinsically at high specific radioac­ tivity. Polypeptides capable of affecting blood pressure or of stimulating smooth muscle are relatively easy to study, and much is known of the clearances, and even the immediate metabolic fates, of bradykinin, the angiotensins, substance P, and vasopressin (cf 28-30, 7 1, 94). However, precise functional assays are not easily developed for other hormones of interest such as parathormone, ACTH, gastrin, proinsulin, C-peptide, and insulin. Similarly, little is known of the fates of other excitatory polypep­ tides (e.g. the anaphylatoxins) during passage through the lungs (cf 17). Radioimmunoassays are available, but these do not help to define function