Free radical scavengers improve the impaired endothelium-dependent responses in aorta and kidneys of diabetic rabbits.
The effects of two endogenous antioxidants, alpha-lipoic acid and reduced gluthathione (GSH), were evaluated in the response of the renal vasculature and aortic rings ex vivo of 4-week alloxan-diabetic rabbits to the endothelium-dependent agonists bradykinin (BK) and acetylcholine (Ach) or to the endothelium-independent agonist sodium nitroprusside (SNP) and compared with age and sex-matched euglycemic rabbits. The maximal decrease in perfusion pressure (R(max)) after BK infusion in the renal vasculature from diabetic rabbits was 5.4+/-1.3% (PD(2) 8 [12.6-3.4]) compared with 34.2+/-4.2% (PD(2) 9 [11.3-6.7]) (P<0.05) attained in tissues obtained from euglycemic rabbits. The addition of 1 microM lipoic acid or GSH improved (P<0.05) the R(max) to BK to 18.3+/-2.4% (PD(2) 8.6 [12.4-4.8]) and 19.5+/-3.7% (PD(2) 9.1 [13.3-4.9]), respectively. Similarly, the maximal vasorelaxant response to Ach in kidneys from diabetic rabbits was 16+/-2.0% (PD(2) 7.3 [10.4-4.2] whilst the R(max) in kidneys from euglycemic animals was 52.7+/-4.9% (PD(2) 11.3 [16.4-6.2]). Incubation with 1 microM alpha-lipoic acid or GSH restored the R(max) to Ach to 31+/-3.9% (PD(2) 9.8 [14.3-5.3]) and to 23+/-5.4% (PD(2) 7.6 [11.4-3.8], respectively. The vasodilatory response to SNP was unaltered among tissues from diabetic and euglycemic rabbits and was also unaffected by the treatments utilized. In addition, the R(max) to Ach in aortic rings of diabetic rabbits was 28.7+/-2.4% (PD(2) 8.3 [11.7-4.9]) compared with 100% (PD(2) 7.9 [12.1-3.7]) obtained in tissues gathered from euglycemic rabbits. The pretreatment of the tissues with alpha-lipoic acid restores the R(max) to 47.4+/-4% (PD(2) 11.1 [14.3-7.9]) and the pretreatment with GSH to 52+/-3.2% (PD(2) 9.8 [12.7-6.9]). Similarly, the response to SNP was unaltered in all groups. Lipoic acid and reduced gluthatione directly improved the endothelium-dependent response of renal arterioles and aortic rings of diabetic rabbits.
Nascimento
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College of Veterinary Medicine, State University of Ceara, PO box 3329, Zip Code 60436-160 Fortaleza, Ceará, Brazil.
Costa-e-Forti
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A
Peter
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Fonteles
Manassés C
MC
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D016166:Free Radical Scavengers; D008063:Thioctic Acid; D005978:Glutathione