AJP - Heart and Circulatory Physiology, Vol 247, Issue 6 999-1004, Copyright © 1984 by American Physiological Society
Amino acids induce renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism
M. Brezis, P. Silva and F. H. Epstein
Renal vasodilatation regularly accompanies protein feeding and amino acid
infusions, but the mechanism is unknown. The effects of several different
amino acids on renal hemodynamics were studied in the isolated rat kidney,
perfused with glucose as the only other substrate. Addition of amino acids
produced a dose-dependent, brisk, and sustained decrease in renal vascular
resistance (by 5-35%) without change in glomerular filtration rate (GFR).
The vasodilatation was associated with a parallel increase in O2
consumption (increases QO2). The effect was most marked with amino acids
actively metabolized by the kidney, such as glutamine (at 2 mM), but was
seen with most amino acids at 8 mM. The amino acid analogues
alpha-aminobutyrate, taurine, and cycloleucine, cotransported with sodium
but not metabolized, did not cause significant vasodilatation or increases
QO2. Blocking active transport with ouabain blunted the amino acid-induced
vasodilatation and increases QO2. Similar resistance to amino acids was
produced by halting GFR with hyperoncotic medium. Restoration of GFR by
increasing perfusion pressure in the presence of hyperoncotic medium
reestablished amino acid-induced vasodilatation and increases QO2.
Furosemide did not block the vasodilatory response. Inhibition of
mitochondrial respiration by antimycin blocked both vasodilatation and
increases QO2, but rotenone blockade could be bypassed by succinate or
glutamine. Amino acids have a direct vasodilating action on isolated
kidneys probably related to their role as metabolic substrates and linked
to an increase in renal O2 consumption.
