AGMATINE AFFECTS GLOMERULAR-FILTRATION VIA A NITRIC-OXIDE SYNTHASE-DEPENDENT MECHANISM

Arginine decarboxylase is present in the kidney and metabolizes the am ino acid, arginine, to agmatine. Agmatine increases filtration rate in single nephrons (J. J. Lortie, W. F. Novotny, O, W. Peterson, V. Vall on, K. Malvey, M. Mendonca, J. Satriano, P. Insel, S. C. Thomson, and R. C. Blantz. J. Clin. Invest. 97: 413-420, 1996). Experiments were co nducted to determine whether exogenously administered agmatine exerts these effects via interaction with nitric oxide synthase (NOS) and whe ther this interaction depends upon alpha(2)-adrenergic receptors. Agma tine microperfused (1 mu M) into the urinary space of surface glomerul i of the rat increased nephron filtration rate from 33 +/- 4 to 40 +/- 5 nl/min with complete recovery within 10 min. When N-G-monomethyl-L- arginine (L-NMMA), a nonselective NOS inhibitor, was systemically infu sed, agmatine no longer increased single-nephron glomerular filtration rate (SNGFR). BHT-933, an alpha(2)-adrenergic agonist, did not increa se SNGFR and was unaffected by concurrent L-NMMA. In vitro incubation of freshly harvested glomeruli with agmatine resulted in significant i ncreases in the generation of cGMP, effects similar to carbachol, and blocked by nitro-L-arginine methyl ester (L-NAME) but not yohimbine, a n alpha(2)-adrenergic antagonist. Agmatine exerts effects on glomerula r ultrafiltration via a constitutive NOS-dependent mechanism, and this does not require the participation of alpha(2)-adrenoreceptors.