l-Arginine inhibits vasopressin-stimulated mesangial cell Ca2.

l-Arginine (l-Arg) affects various parameters that modulate the progression of renal disease. These same factors [e.g., glomerular filtration rate, changes in mesangial cell (MC) tension, and production of NO] are all controlled at least in part by changes in MC intracellular Ca2+concentration ([Ca2+]i). We therefore evaluated the effect of l-Arg on MC [Ca2+]i. We found thatl-Arg inhibits the vasopressin-stimulated rise in MC [Ca2+]i both in rat and murine cell cultures. This effect does not appear to be due to metabolism of l-Arg to either NO or l-ornithine (l-Orn). Blocking the metabolism of l-Arg with N ω-monomethyl-l-arginine, an NO synthase inhibitor, or with 20 mM l-valine (l-Val), an inhibitor of Orn formation, does not reverse the inhibition. However, other cationic amino acids, as well guanidine, the functional group ofl-Arg, all inhibit the vasopressin-stimulated rise in [Ca2+]i, consistent with a structural basis for this effect. We conclude that 1)l-Arg inhibits vasopressin-stimulated murine and rat MC [Ca2+]irise, 2) this inhibition is not mediated by metabolism of l-Arg to either NO or l-Orn, and 3) the effect ofl-Arg is due to its cationic functional group, guanidine.