Mechanisms of glucagon-induced renal vasodilation: role of prostaglandins and endothelium-derived relaxing factor.
The mechanisms underlying the renal hemodynamic responses (vasodilation and hyperfiltration) to an amino acid or protein load are currently unknown and are relevant to understanding the effect of dietary protein on the progression of chronic renal failure. Glucagon (GLC) has been suggested to be important in these renal hemodynamic responses, although the mechanism is again unclear. Thus we investigated potential mediators of the renal hemodynamic response to GLC in the anesthetized rat, including prostanoids and endothelium-derived relaxing factor (EDRF). The effects of glucagon alone and after pretreatment were tested as follows: (1) after baseline renal hemodynamic measurements done with clearance techniques, rats were given GLC alone (n = 5; 200 ng/min IV continuous infusion); (2) glucagon was given after pretreatment with the EDRF synthesis inhibitor nitro-arginine-methyl-ester (NAME; n = 6; 125 micrograms/kg/min intrarenal artery by continuous infusion); (3) glucagon was given after pretreatment with indomethacin (INDO; n = 6; 5 mg/kg IV bolus). Repeat clearances demonstrated that GLC infusion increased glomerular filtration rate (GFR; basal vs GLC, 0.87 +/- 0.04 ml/min vs 1.14 +/- 0.09 ml/min, p < 0.05); renal plasma flow (RPF; 4.10 +/- 0.18 ml/min vs 5.56 +/- 0.32 ml/min, p < 0.05) and decreased renal vascular resistance (RVR; 15.82 +/- 1.17 mm Hg/[ml/min] vs 10.72 +/- 0.65 mm Hg/[ml/min], p < 0.05). Intrarenal N-nitro-L-arginine-methyl-ester (NAME) infusion significantly reduced basal GFR (-20% +/- 8%, p < 0.05) and RPF (-43% +/- 2%, p < 0.05), while increasing RVR (+108% +/- 9%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Tolins
J P
JP
Department of Medicine, University of Minnesota School of Medicine.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D011453:Prostaglandins; D009569:Nitric Oxide; D005934:Glucagon; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin