Renal uptake and excretion of homocysteine in rats with acute hyperhomocysteinemia.
BACKGROUND
Elevated plasma total homocysteine, an independent risk factor for cardiovascular disease, is commonly observed in renal patients. We have previously shown that the kidney is a major site for the removal of plasma homocysteine in the rat. The present investigation was performed to further characterize the capacity of the kidney to handle acute elevations in plasma homocysteine concentrations.


METHODS
Acute hyperhomocysteinemic conditions (4- to 7-fold > controls) in rats were produced by either a primed-continuous infusion of L-homocysteine or exposure to 80:20% nitrous oxide:oxygen, which results in the inhibition of methionine synthase.


RESULTS
At physiological homocysteine concentrations, approximately 15% of the arterial plasma homocysteine was removed on passage through the kidney. Renal homocysteine uptake was approximately 85% of the filtered load. The urinary excretion of homocysteine was negligible (<2%). During acute hyperhomocysteinemia produced by the infusion of L-homocysteine, renal homocysteine uptake was increased fourfold and was equivalent to 50% of the infused dose, while urinary excretion remained negligible. Renal homocysteine uptake during nitrous oxide-induced hyperhomocysteinemia increased threefold, with urinary excretion remaining negligible.


CONCLUSIONS
These results provide strong evidence that the kidney has a significant capacity for metabolizing acute elevations in plasma homocysteine, and support a very limited role for the re-methylation pathway in renal homocysteine metabolism.
House
J D
JD
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Brosnan
M E
ME
Brosnan
J T
JT
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D006439:Hemodynamics; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D006710:Homocysteine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase