Influence of aldose reductase inhibition on the microvascular reactivity in experimental diabetes.
1. To verify if tolrestat, an aldose reductase inhibitor, corrects the impaired responses of microvessels to histamine and bradykinin in alloxan-diabetic rats, the mesenteric microcirculation was studied in vivo in anaesthetised animals. 2. The impaired responses were corrected by tolrestat 5 mg/kg/day for 7 days p.o. Similar responses to acetylcholine and sodium nitroprusside were obtained in preparations of diabetic and control rats and were not altered by tolrestat treatment. 3. As in diabetes, galctosemia induced impaired responses to histamine and bradykinin; these altered responses were corrected by tolrestat treatment. 4. These data allow us to suggest that the polyol pathway activity might be involved in the altered responses of microvessels observed in diabetic rats. It is possible that polyol activation may play an important role in the development of vascular dysfunction in diabetes mellitus.
Fortes
Z B
ZB
Dept. of Pharmacology, University of São Paulo, Brazil.
Becker
C
C
Oliveira
M A
MA
Scivoletto
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects; D014699:Venules / Q000187:drug effects
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D009281:Naphthalenes; C040550:tolrestat; D009599:Nitroprusside; D006632:Histamine; D000449:Aldehyde Reductase; D000109:Acetylcholine; D001920:Bradykinin