The renal natriuretic peptide urodilatin is present in human kidney

Background. The natriuretic peptide urodilatin was first isolated from human urine and may be one of the important mediators of natriuresis, while the atrial natriuretic peptide alpha-ANP, the circulating member of the family, rather seems to play a role in cardiovascular regulation. Although the renal expression of the common propeptide for urodilatin and alpha-ANP has been detected in rat and pig, it is not yet shown that urodilatin is synthesized in human kidney. Methods. Immunhistochemically we localized urodilatin with an urodilatin-antibody, which does not cross-react with alpha-ANP, the ANP propeptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Radiolabelled urodilatin binding was examined autoradiographically. Results. We could demonstrate that urodilatin is present in human distal tubular cells, in which we could also localize propeptide immunoreactivity. The glomeruli, the cells of the proximal tubule, and the collecting duct did not show any urodilatin immunoreactivity. In human kidney homogenate the urodilatin content was 4600 +/- 520 fmol/g protein (n = 6). The renal concentration of BNP and CNP, mainly localized in the distal tubule, was much lower at 40 +/- 8 and 400 +/- 50 fmol/g protein (n=6) respectively. Furthermore the autoradiographic examinations showed that radiolabelled urodilatin binds to natriuretic peptide receptors in the glomeruli, blood vessels, and collecting ducts. Conclusions. Our data suggest that urodilatin may be the predominant representative of natriuretic peptides in human kidneys. Urodilatin being synthesized in the distal tubular region may be transported as a paracrine factor to the collecting duct, where it exerts its suppressing effect on the sodium reabsorption by stimulating the guanylyl cyclase A.