Effects of aldose reductase inhibition on responses of the corpus cavernosum and mesenteric vascular bed of diabetic rats.
We examined the effects of 2 months of streptozotocin-induced diabetes mellitus in rats on relaxation and contraction of corpus cavernosum and the mesenteric vascular bed in vitro. A further diabetic group was treated from diabetes induction with 10 mg/kg/day of the aldose reductase inhibitor, WAY121509. For corpus cavernosum, maximal acetylcholine-induced relaxation was 35.5% reduced (p < 0.001) by diabetes, and this deficit was completely prevented by WAY121509 treatment. Neither diabetes nor treatment affected contractile responses to field stimulation of noradrenergic nerves; however, nonadrenergic noncholinergic nerve relaxation responses were 32.9% decreased by diabetes and WAY 121509 attenuated this by 84% (p < 0.001). For the mesenteric vascular bed, diabetes depressed maximal endothelium-dependent vasodilation to acetylcholine by 25.2% (p < 0.001), and this was partially (50.6%; p < 0.01) prevented by WAY121509. Nitric oxide synthase blockade revealed endothelium-derived hyperpolarising factor-mediated vasodilation to acetylcholine that was 73.5% (p < 0.001) depressed by diabetes; WAY121509 provided partial (43.4%; p < 0.001) protection. Neither diabetes nor treatment affected endothelium-independent vasorelaxation to the nitric oxide donor, sodium nitroprusside, in corpus cavernosum or mesenteric vessels. Thus the data show protective effects of WAY121509 on nitric oxide-mediated cavernosal vasorelaxation responses and on mesenteric endothelium-derived hyperpolarising factor responses. Together these findings could account for the beneficial effects of aldose reductase inhibition on diabetic complications in experimental models.
Keegan
A
A
Department of Biomedical Sciences, University of Aberdeen, Scotland.
Jack
A M
AM
Cotter
M A
MA
Cameron
N E
NE
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects*; D010413:Penis / Q000098:blood supply* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; C091470:WAY 121-509; D000449:Aldehyde Reductase