A lack of direct action of glucagon on kidney metabolism, hemodynamics, and renal sodium handling in the dog

Abstract

Although several reports suggest that pharmacologic amounts of glucagon may promote natriuresis, the influence of a physiological or even pathophysiological increase in circulating glucagon levels on kidney function has never been convincingly demonstrated. The present study was therefore undertaken to determine whether a moderate increase in plasma glucagon concentration of blood perfusing the kidney may influence kidney function and promote urinary sodium excretion. To this end, glucagon was infused directly into one renal artery of anesthetized dogs at a rate of 1 ng x kg(-1) x min(-1), calculated to increase glucagon concentration in the blood perfusing the kidney within the pathophysiologic range and thus to levels seen in some catabolic states such as poorly controlled diabetes or starvation. The contralateral kidney was infused with saline only. The estimated concentration of glucagon in blood perfusing the hormone-infused kidney increased with glucagon infusion from 227 pg x mL(-1) during the control period to mean of 779 pg x mL(-1). There was a significant increase in glucagon extraction by this kidney, from 33% in baseline conditions to 61% upon intrarenal infusion of the hormone, and hence venous glucagon levels were only slightly higher than in the contralateral kidney. Despite a more than threefold increase in glucagon levels in blood perfusing the hormone-infused kidney versus the contralateral kidney, this experimentally induced hyperglucagonemia was without influence on renal plasma flow (RFP), glomerular filtration rate (GFR), renal vascular resistance, renal uptake of oxygen and energy-providing substrates. Excretion of Na+, K+, Cl-, and PO4(3-) was likewise unaffected. These results indicate that hyperglucagonemia, at least of a magnitude comparable to that seen in starvation or diabetic decompensation, is devoid of any detectable direct influence on renal hemodynamics or tubular function.