Biosynthesis and secretion of adrenomedullin and proadrenomedullin N-terminal 20 peptide in a rat model of endotoxin shock

To study the biosyntheses and pathophysiological roles of adrenomedullin (A M) and proadrenomedullin N-terminal 20 peptide (PAMP) in septic shock, we c ompared the time course of plasma concentrations of these peptides and bloo d pressure in rats injected with either 0.9% saline (control group) or lipo polysaccharide (LPS group). The plasma AM concentration in the LPS group di d not increase 30 and 60 min after LPS injection, at which time points the blood pressure remained low. Thereafter, AM rapidly increased, and it amoun ted to 35 times the basal value 4 h after injection, when the blood pressur e returned to the basal level. The increment of plasma PAMP in the LPS grou p was lower than that of AM. We also examined the tissue concentration of A M and PAMP-as well as the tissue expression of proadrenomedullin (proAM) mR NA-in the LIPS and control groups. LIDS significantly increased the tissue concentrations of AM and PAMP in the lung, but decreased them in the adrena l gland and cardiac atrium. The LPS injection augmented proAM gene transcri ption in the lung, adrenal gland and aorta. In an immunohistochemical exami nation, AM staining was intense in alveolar endothelial cells of the lung i n the LPS group. Thus, this septic shock model had high plasma levels of PA MP as well as AM, while the biosynthesis and secretion of the two peptides may have been differentially regulated in various tissues of rats injected with LPS. The present results suggest that these two bioactive peptides may play different roles in the pathophysiology of septic shock.