The effect of glucagon on glomerular filtration rate in dogs during reduction of renal blood flow.
Glucagon in small intravenous (i.v.) doses markedly increases glomerular filtration rate (GFR) in normal anesthetized dogs. In this study, the effects of glucagon 5 mug/min (i.v.) on renal hemodynamics was tested in four canine models of acute pre-renal failure (hemorrhage, barbiturate overdose; renal arterial clamping and renal arterial infusions of noradrenaline) and in a model of unilateral acute tubular necrosis at 4 h and 6-7 days following completion of the ischemic insult. Following hemorrhage and barbiturate excess, with arterial blood pressure maintained at 65-70 mm Hg, whole-kidney GFR and clearance rate of p-aminohippurate decreased by 50-70%. During this reduction of perfusion pressure, the subsequent infusion of glucagon increased GFR by 90-130%. In models where arterial pressure was normal during the period of ischemia (clamping and noradrenaline infusion), not only did glucagon significantly increase renal perfusion, but the ischemic kidney proved to be far more sensitive to the hemodynamic effects of glucagon (delta GFR - 120-160%) than the contralateral control (deltaGFR = 30-40%). In three dogs completely anuric following renal arterial clamping, glucagon was able to improve blood flow and restart urine formation. Glucagon, but not dopamine, was able to simulate the beneficial effects of hypertonic mannitol on renal function in dogs with hemorrhagic hypotension. Glucagon was without effect in established acute tubular necrosis. This study, therefore, indicates that, during renal ischemia, glucagon may be quite effective in preserving urine output and perfusion of the kidneys.
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005934:Glucagon / Q000494:pharmacology*; D006470:Hemorrhage / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D007683:Kidney Tubular Necrosis, Acute / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000502:physiology; D013997:Time Factors
D001463:Barbiturates; D005934:Glucagon; D009638:Norepinephrine