Glucagon and prostaglandins are mediators of amino acid-induced rise in renal hemodynamics.
An oral protein load or infusion of amino acids induces a rise in renal hemodynamics in normal subjects, but the mechanisms mediating this phenomenon are unknown. We investigated whether glucagon may mediate the increase in RPF and GFR induced by an arginine infusion and whether prostaglandins are required for this effect. In four different studies, normal subjects underwent 13 inulin and PAH clearances of 30 minutes each. During the fourth and tenth clearance periods arginine HCl, 250 mg/kg, was infused over 30 minutes. At the beginning of the fifth clearance period several subjects ingested indomethacin, 150 mg, (N = 8) or ibuprofen, 800 mg (N = 6). Control subjects (N = 4) did not receive cyclooxygenase inhibitors. Six subjects underwent a similar protocol except that they were infused with glucagon, 6 ng/kg/min, instead of arginine, for 30 minutes during the fourth and tenth periods. They also ingested indomethacin, 150 mg, in the fifth period. In all four studies, a transient and significant rise in RPF and GRF and fall in RVR occurred during the first arginine or glucagon infusion. These changes in renal hemodynamics were blocked when the arginine or glucagon infusion was repeated after administration of indomethacin or ibuprofen. Urinary excretion of 6-keto-PGF1 alpha did not rise with either arginine infusion in the control subjects or in the individuals who received indomethacin. As predicted, urinary 6-keto-PGF1 alpha fell significantly after ingestion of indomethacin before the second infusion of arginine. Plasma norepinephrine and epinephrine concentrations were unaffected by the arginine infusions or by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirschberg
R R
RR
Division of Nephrology, Harbor-UCLA Medical Center, Torrance.
Zipser
R D
RD
Slomowitz
L A
LA
Kopple
J D
JD
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D000596:Amino Acids / Q000494:pharmacology*; D001120:Arginine; D005260:Female; D005919:Glomerular Filtration Rate; D005934:Glucagon / Q000502:physiology*; D006801:Humans; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D012079:Renal Circulation
D000596:Amino Acids; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D005934:Glucagon; D001120:Arginine