This study examined the importance of changes in renal hemodynamics and renal artery pressure (RAP) in allowing the kidneys to escape from the chronic sodium-retaining effects of aldosterone (Aldo). In five dogs in which RAP was permitted to increase during Aldo infusion (14 micrograms/kg/day), sodium excretion (UNaV) and fractional sodium excretion (FENa) decreased markedly on Day 1 and then returned to control on Days 2 to 4 of Aldo infusion as RAP and glomerular filtration rate (GFR) increased 15 to 19 mm Hg and 20% to 24%, respectively, and remained near these levels during 7 days of Aldo infusion. In seven dogs in which RAP was prevented from increasing with an electronically servo-controlled aortic occluder, UNaV decreased from 256 +/- 3 to 117 +/- 9 mEq/day on the first day and remained at 70 to 80 mEq/day below sodium intake for 7 days of Aldo infusion. Cumulative sodium balance and sodium iothalamate space increased 610 +/- 39 mEq and 3729 +/- 397 ml when RAP was servo-controlled, causing ascites in most of the dogs, while mean arterial pressure did not plateau but continued to rise to 59 +/- 3 mm Hg above control after 7 days of Aldo infusion. When the servo-controller was stopped and RAP was allowed to rise while Aldo infusion was continued, GFR rose to 126% to 136% of control, FENa increased markedly, UNaV increased to 579 +/- 64 mEq/day on the first day, and the dogs returned to normal sodium balance. These data indicate that an increase in RAP, which raises GFR and FENa, is essential in allowing the kidneys to escape from the chronic sodium-retaining action of Aldo and to achieve sodium balance and a stable level of arterial pressure without severe volume expansion and ascites.

No abstract

The aim of this study was to ascertain the quantitative importance of glucagon in mediating protein-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR) during the postprandial state. Six chronically instrumented conscious dogs were each subjected to four protocols: normal protein control meal (C); high protein meat meal (M); somatostatin infusion and meat (S + M); and glucagon infusion. C produced small increases in RBF (12 +/- 2%) and GFR (14 +/- 2%) without changing arterial plasma glucagon. M produced marked increases in RBF (38 +/- 4%), GFR (41 +/- 5%), and glucagon (from 23.3 +/- 3.6 to 73.3 +/- 7.1 pg/ml) over a 3-h period. During S + M, RBF and GFR failed to increase while glucagon was suppressed by 36 +/- 8% over a 2-h period. When S was stopped, glucagon rose to 100 +/- 13.9 pg/ml over the next hour, yet RBF and GFR increased by only 14 +/- 4 and 10 +/- 3%, respectively. Glucagon infusion (3 ng X kg-1 X min-1, i.v.) markedly elevated plasma glucagon to 131.6 +/- 27.3 pg/ml, yet neither RBF nor GFR significantly changed. These data indicate that while a protein-rich meat meal does elevate arterial plasma glucagon, the rise is not great enough to elicit significant changes in renal hemodynamics. Thus, elevated plasma levels of glucagon cannot account for protein-mediated increases in RBF and GFR during the postprandial state.

The role of glucagon as a blood-borne mediator of the hyperdynamic circulation associated with chronic portal venous hypertension was assessed in the rat portal vein stenosis model. Selective removal of pancreatic glucagon from the circulation was achieved by intravenous infusion of a highly specific glucagon antiserum. Blood flow to splanchnic organs, kidneys, and testicles was measured with radioactive microspheres, and the reference-sample method. Glucagon antiserum had no effect on blood flow in the gastrointestinal tract of sham-operated (control) rats. However, the antiserum produced a significant reduction in hepatic arterial blood flow in the control rats, suggesting that glucagon contributes significantly to the basal tone of hepatic arterioles. In portal hypertensive rats glucagon antiserum significantly reduced blood flow to the stomach (22%), duodenum (25%), jejunum (24%), ileum (26%), cecum (27%), and colon (26%). Portal venous blood flow was reduced by approximately 30%. The results of this study support the hypothesis that glucagon mediates a portion of the splanchnic hyperemia associated with chronic portal hypertension.

Although the existence of postprandial renal hyperemia and hyperfiltration has been established, the precise mechanism governing protein-mediated increases in renal hemodynamics is not, as yet, clearly defined. Investigative effort over the past decade has provided at least two plausible mechanisms playing an important role in renal hyperemia and hyperfiltration associated with ingestion of a protein-rich meal: 1) blood-borne vasoactive agents (e.g., pancreatic glucagon and/or hepatic glomerulopressin); and 2) intrarenal mechanisms (e.g., the tubuloglomerular feedback system). Data supporting each of these two candidate mechanisms are reviewed as are data supporting the importance of other factors such as renal prostanoids, the renin-angiotensin system, and renal cyclic nucleotides. It is anticipated that future investigative effort will be stimulated by our present knowledge of postprandial renal hemodynamics so that one day we not only will know the precise mechanisms governing postprandial renal hyperemia and hyperfiltration but, in addition, may gain valuable insight into the pathogenesis of chronic renal disease.