INFLUENCE OF GLUCAGON ON GFR AND ON UREA AND ELECTROLYTE EXCRETION - DIRECT AND INDIRECT EFFECTS

Clearance experiments were performed in anesthetized male Wistar rats to determine the level of peripheral glucagon concentration required t o elicit changes in glomerular filtration rate (GFR) and in solute exc retion. Glucagon was intravenously infused at a rate of 1.25 (group G- 1, n = 8), 3.75 (group G-3, n = 7), or 12.5 (group G-10, n = 7) ng . m in(-1) . 100 g body wt(-1) for 100 min. Measurements were performed be fore, during, and after this infusion. Group G-10 resulted in a plasma concentration of glucagon severalfold higher than usually observed in peripheral blood after a protein meal but normal for the hepatic circ ulation. Group G-10 simultaneously increased GFR, plasma adenosine 3', 5'-cyclic monophosphate (cAMP) concentration, and the excretion of wat er (i.e., urinary flow rate), Na, Cl, PO4, K, and urea. Some of the ef fects of glucagon on electrolyte excretion were also observed with gro up G(-1) and/or G-3 and were fully reversible, suggesting a direct ren al action of glucagon. The significant and reversible increase in K ex cretion in group G-3 suggests that glucagon exerts a direct stimulator y influence on K secretion in the distal nephron. Increases in urinary flow rate, PO4, Na, and urea fractional excretions were seen with gro up G-10 only and were not reversible, suggesting an indirect action of glucagon on the proximal tubule. Because glucagon stimulates cAMP for mation in hepatocytes and because this cAMP is released in the blood a nd secreted by proximal tubule cells, cAMP of hepatic origin could ind uce a parathyroid hormone-like effect in this nephron segment. In summ ary, these experiments suggest that glucagon influences different aspe cts of renal function by a combination of direct and indirect (probabl y liver-dependent) effects.