Agmatine affects glomerular filtration via a nitric oxide synthase-dependent mechanism.
Arginine decarboxylase is present in the kidney and metabolizes the amino acid, arginine, to agmatine. Agmatine increases filtration rate in single nephrons (J. J. Lortie, W. F. Novotny, O. W. Peterson, V. Vallon, K. Malvey, M. Mendonca, J. Satriano, P. Insel, S. C. Thomson, and R. C. Blantz. J. Clin. Invest. 97:413-420, 1996). Experiments were conducted to determine whether exogenously administered agmatine exerts these effects via interaction with nitric oxide synthase (NOS) and whether this interaction depends upon alpha 2-adrenergic receptors. Agmatine microperfused (1 microM) into the urinary space of surface glomeruli of the rat increased nephron filtration rate from 33 +/- 4 to 40 +/- 5 nl/min with complete recovery within 10 min. When NG-monomethyl-L-arginine (L-NMMA), a nonselective NOS inhibitor, was systemically infused, agmatine no longer increased single-nephron glomerular filtration rate (SNGFR). BHT-933, an alpha 2-adrenergic agonist, did not increase SNGFR and was unaffected by concurrent L-NMMA. In vitro incubation of freshly harvested glomeruli with agmatine resulted in significant increases in the generation of cGMP, effects similar to carbachol, and blocked by nitro-L-arginine methyl ester (L-NAME) but not yohimbine, an alpha 2-adrenergic antagonist. Agmatine exerts effects on glomerular ultrafiltration via a constitutive NOS-dependent mechanism, and this does not require the participation of alpha 2-adrenoreceptors.
Schwartz
D
D
Division of Nephrology-Hypertension, University of California, School of Medicine, La Jolla 92093, USA.
Peterson
O W
OW
Mendonca
M
M
Satriano
J
J
Lortie
M
M
Blantz
R C
RC
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D015398:Signal Transduction; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D019323:omega-N-Methylarginine; D000376:Agmatine; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP