A LACK OF A DIRECT ACTION OF GLUCAGON ON KIDNEY METABOLISM, HEMODYNAMICS, AND RENAL SODIUM HANDLING IN THE DOG

Although several reports suggest that pharmacologic amounts of glucago n may promote natriuresis, the influence of a physiological or even pa thophysiological increase in circulating glucagon levels on kidney fun ction has never been convincingly demonstrated. The present study was therefore undertaken to determine whether a moderate increase in plasm a glucagon concentration of blood perfusing the kidney may influence k idney function and promote urinary sodium excretion. To this end, gluc agon was infused directly into one renal artery of anesthetized dogs a t a rate of 1 ng . kg(-1). min(-1), calculated to increase glucagon co ncentration in the blood perfusing the kidney within the pathophysiolo gic range and thus to levels seen in some catabolic states such as poo rly controlled diabetes or starvation. The contralateral kidney was in fused with saline only. The estimated concentration of glucagon in blo od perfusing the hormone infused kidney increased with glucagon infusi on from 227 pg . mL(-1) during the control period to mean of 779 pg . mL(-1). There was a significant increase in glucagon extraction by thi s kidney, from 33% in baseline conditions to 61% upon intrarenal infus ion of the hormone, and hence venous glucagon levels were only slightl y higher than in the contralateral kidney. Despite a more than threefo ld increase in glucagon levels in blood perfusing the hormone-infused kidney versus the contralateral kidney, this experimentally induced hy perglucagonemia was without influence on renal plasma flow (RPF), glom erular filtration rate (GFR), renal vascular resistance, renal uptake of oxygen and energy-providing substrates. Excretion of Na+, K+, Cl-, and PO43- was likewise unaffected. These results indicate that hypergl ucagonemia, at least of a magnitude comparable to that seen in starvat ion or diabetic decompensation, is devoid of any detectable direct inf luence on renal hemodynamics or tubular function. Copyright (C) 1996 b y W.B. Saunders Company