PLASMA CAMP - A HEPATORENAL LINK INFLUENCING PROXIMAL REABSORPTION AND RENAL HEMODYNAMICS

The existence of a hepatorenal link is suggested by several pathophysi ological observations (indirect actions of glucagon on the kidney, hep atorenal syndrome), but the nature of this link; remains unidentified. We propose that extracellular circulating cyclic AMP could be this li nk. Cyclic AMP (cAMP) is the intracellular second messenger of glucago n (G) action in the liver, and this organ is known to release cAMP in the blood in relatively large amounts after G administration. On thr o ther hand, the proximal tubule (mainly the pars rectal is known to tak e up cAMP through,ugh the organic acid transport system. We observed t hat the glucagon-induced rise in phosphate excretion, which requires s upraphysiologic concentration of tr, was significantly correlated with the simultaneous rise in plasma cAMP and could be mimicked by i.v. in fusion of cAMP alone. Moreover, we showed that a significant hyperfilt ration (similar to that induced by supraphysiologic G) can be observed if cAMP (mimicking G-induced hepatic release) is coinfused with a muc h lower. physiologic, amount of G. Taken together, these observations suggest that: (1) cAMP is a hepatorenal link and that plasma cAMP perm anently influences the intensity of reabsorption in the pars recta of the proximal tubule; and (2) that cAMP participates, in conjunction wi th G, to control GFR. Insulin is known to exert an inhibitory influenc e on G-induced cAMP release by the liver and will thus weaken the indi rect (cAMP-mediated) influence of G on renal function. This ''pancreat o-hepatorenal cascade'' may explain the natriuretic effects of G and a ntinatriuretic effects of insulin, and probably contributes to disturb ances observed in some pathophysiological situations such as the edema of liver cirrhosis or hyperfiltration of diabetes.