Antioxidant N-acetylcysteine restores systemic nitric oxide availability and corrects depressions in arterial blood pressure and heart rate in diabetic rats.
Increased oxidative stress and reduced nitric oxide (NO) bioactivity are key features of diabetes mellitus that eventually result in cardiovascular abnormalities. We assessed whether N-acetylcysteine (NAC), an antioxidant and glutathione precursor, could prevent the hyperglycaemia induced increase in oxidative stress, restore NO availability and prevent depression of arterial blood pressure and heart rate in vivo in experimental diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were treated or not treated with NAC in drinking water for 8 weeks, initiated 1 week after induction of diabetes. At termination, plasma levels of free 15-F2t-isoprostane, a specific marker of oxygen free radical induced lipid peroxidation, was increased while the plasma total antioxidant concentration was decreased in untreated diabetic rats as compared to control rats (P<0.05). This was accompanied by a significant reduction of plasma levels of nitrate and nitrite, stable metabolites of NO, (P<0.05, D vs. C) and a reduced endothelial NO synthase protein expression in the heart and in aortic and mesenteric artery tissues. Systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP) and heart rate (HR) were reduced in diabetic rats (P<0.05 vs. C) and NAC normalised the changes that occurred in the diabetic rats. The protective effects may be attributable to restoration of NO bioavailability in the circulation.
Xia
Zhengyuan
Z
Faculty of Pharmaceutical Sciences, The University of British Columbia, Division of Pharmacology, 2146 East mall, Vancouver BC, V6T 1Z3, Canada.
Nagareddy
Prabhakara R
PR
Guo
Zhixin
Z
Zhang
Wei
W
McNeill
John H
JH
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000517:prevention & control; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D015227:Lipid Peroxidation; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D014662:Vasoconstrictor Agents / Q000097:blood
D000975:Antioxidants; D005609:Free Radicals; D009566:Nitrates; D009573:Nitrites; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D013311:Streptozocin; D015237:Dinoprost; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000111:Acetylcysteine