The importance of the liver in mediating protein-induced elevations in renal and intestinal hemodynamics will be assessed. Under pentobarbital anesthesia, a large splenic vein and the superior mesenteric artery (SMA) will be isolated in anesthetized dogs. The splenic vein will be cannulated for intraportal infusions of various vasoactive substances known to be elevated in the circulation following a high protein meal (e.g., amino acids and endogenous hormones). A flow probe will be placed around the SMA to continuously monitor intestinal blood flow. the left kidney will be isolated and a flow probe placed around the renal artery to monitor renal blood flow. The renal vein will be cannulated, via the gonadal vein, in order to obtain venous blood for measurement of glomerular filtration rate (GFR). GFR will be calculated from the renal arterio-venous extraction of sodium iothalamate. Intravenous infusion of the test substances will serve as appropriate controls for each series. Arterial pressure, heart rate, plasma protein concentration, plasma glucose, and arterial hematocrit will be periodically measured in all studies. The following series of experiments are proposed: 1) Intravenous versus intraportal infusion of physiological concentrations of pancreatic glucagon; 2) Intravenous versus intraportal infusion of physiological concentrations of different amino acids; 3) Additive and/or synergistic effects of amino acids and glucagon on hemodynamics; 4) Intravenous versus intraportal infusion of different gastrointestinal hormones known to be elevated in the circulation after protein intake; 5) Additive and/or synergistic effects of GI hormones and glucagon on blood flow; 6) Additive and/or synergistic effects of GI hormones and amino acids on blood flow; 7) Additive and/or synergistic effects of GI hormones, glucagon, and amino acids on blood flow. It is anticipated that these studies will not only further our understanding of digestive and renal physiology but, may add some insight into the etiology of a pathophysiologic state known to involve interactions between the gastrointestinal tract/liver and the kidneys, i.e., the progression to end stage renal failure that has recently been attributed to long-term ad libitum protein intake.
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