Lack of effect of diet-induced hypomethylation on endothelium-dependent relaxation in rats.
BACKGROUND
Endothelial dysfunction is a key process in atherosclerosis. Hypomethylation is one of the postulated mechanisms involved in atherogenesis and is mainly secondary to a decrease in essential factors such as, folate and vitamin B12 for the biosynthesis of S-adenosylmethionine (SAM), the main methyl-group donor for methylation reactions.


OBJECTIVE
To investigate in an animal model, whether hypomethylation, secondary to folate or vitamin B12 deficiency, affects endothelium-dependent relaxation (EDR) induced by acetylcholine (ACh).


METHODS
Adult male Wistar rats were divided into 4 groups of 12 rats each: folate and B12 deficiency (FB12D 0mg folate/kg, 0 microg/kg B12), folate deficiency (FD 0mg folate/kg and 50 microg/kg B12), B12 deficiency (B12D: 8 mg/kg folate and 0 microg/kg B12 and control diet (CD)). After eight weeks the animals were killed and thoracic aorta and liver removed. Serum concentration of homocysteine, folate and vitamin B12 were determined. Hepatic levels of SAM and S-adenosylhomocysteine (SAH) were measured, as indicator of hypomethylation. ACh-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR), in isolated aorta rings were evaluated.


RESULTS
Hcy concentrations were significantly increased in the folate and B12 deficient groups. SAM and the SAM/SAH ratio were lower in the FD and FB12D than in the control and B12D group. Folate, B12 deficiency, serum Hcy levels and hepatic SAM/SAH ratio did not affect EDR neither EIR.


CONCLUSIONS
In adult Wistar rats, chronic folate or folate plus vitamin B12 deficiency generates hypomethylation which is not related to an alteration of endothelial function.
Aging and chronic diseases program, INTA, University of Chile, PO Box 138-11, Santiago, Chile. shirsch@inta.cl
Sandra
S
Hirsch
Ana María
AM
Ronco
Gianni
G
Pinardi
María José
MJ
Montequin
Laura
L
Leiva
María Pía
MP
de la Maza
Miguel
M
Llanos
Daniel
D
Bunout
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005494:Folic Acid Deficiency / Q000378:metabolism* / Q000503:physiopathology; D006710:Homocysteine / Q000097:blood; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000378:metabolism* / Q000503:physiopathology
D020030:Nitric Oxide Donors; D006710:Homocysteine; D009599:Nitroprusside; D012436:S-Adenosylmethionine; D000109:Acetylcholine; D014805:Vitamin B 12