Impaired contraction and relaxation in aorta from streptozotocin-diabetic rats: role of polyol pathway.
The effects of 3 months streptozotocin-induced diabetes mellitus on contraction and relaxation of aorta were examined in vitro. A further diabetic group was treated with a novel sulphonylnitromethane-based aldose reductase inhibitor for 3 months following diabetes induction. Diabetes resulted in reduced maximal tension production, particularly for responses to phenylephrine (p < 0.001) and serotonin (p < 0.001). However, with aldose reductase inhibitor treatment, responses were in the non-diabetic range. The ratio of maximum contractions to noradrenaline and phenylephrine were 28% elevated by diabetes (p < 0.01), which may suggest increased alpha 2-adrenoreceptor-mediated responses. Endothelium-independent relaxation to glyceryl trinitrate was unaffected by diabetes or treatment. By contrast, there were 38% deficits in endothelium-dependent relaxation to acetylcholine (p < 0.001) and Ca2+ ionophore A23187 (p < 0.001) with diabetes which were prevented by aldose reductase inhibitor treatment (p < 0.001). A 121% shift in the concentration giving a 50% maximum effect for acetylcholine towards lower sensitivity with diabetes (p < 0.001) was also largely corrected by treatment (p < 0.001). A non-diabetic group treated with aldose reductase inhibitor showed a 30% decrease in the 50% effective concentration for acetylcholine (p < 0.05). A 15% deficit in maximum relaxation to the ATP-sensitive K+ channel opener cromakalim for the diabetic group (p < 0.001) was prevented by aldose reductase inhibitor treatment (p < 0.01). We conclude that there are polyol pathway related abnormalities for contraction, some aspects of endothelium-independent relaxation, but particularly for endothelium-dependent relaxation in aorta from chronic streptozotocin-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Cameron
N E
NE
Department of Biomedical Sciences, University of Aberdeen, UK.
Cotter
M A
MA
D000665:Ampholyte Mixtures; D000818:Animals; D001013:Aorta, Thoracic; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D000665:Ampholyte Mixtures; D011108:Polymers; C024617:polyol; D013311:Streptozocin