Contraction and relaxation of aortas from galactosaemic rats and the effects of aldose reductase inhibition.
Rats were fed for 10 days with a 40% galactose diet, in order to chronically stimulate the polyol pathway. Thoracic aorta contraction and relaxation were studied. Compared to controls, galactosaemia did not influence contractions to phenylephrine or serotonin. Acetylcholine produced concentration-dependent relaxation of aortic rectangles precontracted with phenylephrine; galactosaemia caused a 25% deficit in maximum relaxation to acetylcholine (P < 0.01) and a 168% increase in EC50. There was a similar 25% reduction in relaxation to 3 microM calcium ionophore A23187 (P < 0.05). By contrast, there were no significant differences in endothelium-independent relaxation to nitroglycerine or cromakalim. The abnormalities in endothelium-dependent relaxation were completely prevented by treating galactosaemic rats with the aldose reductase inhibitor, ponalrestat. Thus, the data demonstrate that elevated polyol pathway activity contributes to reduced endothelium production, release or the action of nitric oxide in experimental galactosaemia, and suggest that this mechanism could also contribute to the vascular defects seen in diabetes mellitus.
Cameron
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NE
Department of Biomedical Sciences, University of Aberdeen, Marischal College, Scotland, UK.
Cotter
M A
MA
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000503:physiopathology; D005693:Galactosemias / Q000503:physiopathology*; D008297:Male; D010793:Phthalazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D010793:Phthalazines; C042829:ponalrestat; D000449:Aldehyde Reductase