Abstract
In our study, the effects of glycosylated protein cross-link breaker, alagebrium was investigated on isolated rat carotid artery using myography. Alagebrium showed vasodilator effect on carotid artery rings; particularly, this effect was significantly increased in endothelium-intact rings. To clarify the vasodilator mechanism of alagebrium, different antagonists such as N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, indomethacin, metoprolol, propranolol, tetraethylammonium, and calcium channel activator BAYK-8644 were used to reverse this effect. Relaxation% responses to alagebrium were more significantly increased in intact endothelium than in denuded arteries. Blocking vasodilation related to channels (K-ATP, PGI2, BKca) and receptors (ß1, ß2) did not reverse the relaxation response to alagebrium. Vasodilator response to alagebrium was only slightly decreased after L-NAME incubation and significantly decreased after BAYK-8644 incubation. Results of present study suggest that the mechanism of alagebrium-induced vasodilator effect may include the blockage of L-type calcium channels and partially of the nitric oxide synthase enzyme.
Highlights
Advanced glycation end-products (AGEs) are harmful substances produced by non-enzymatic glycation of reducing sugars
Responses of isolated rat carotid artery to alagebrium response to alagebrium in arteries precontracted with PE after incubation with L-NAME Normal relaxation responses to alagebrium as well as relaxation responses to alagebrium after incubation with L-NAME were assessed in endothelium-intact (Et(+)) and endothelium-removed (Et(−)) arterial rings
Relaxation response to cumulative doses of alagebrium in Et(+) and Et(−) vessels precontracted with PE Effect of cumulative doses of alagebrium (10−10 to 10−3 M) was assessed in carotid arteries precontracted with PE
Summary
Advanced glycation end-products (AGEs) are harmful substances produced by non-enzymatic glycation of reducing sugars. Glycation is initiated by non-enzymatic reaction of the compounds having a carbonyl group with the amino group of proteins, nucleic acids, and lipids. Glycation products, including reactive oxygen species (ROS), produced by oxidation reaction are transformed into AGEs by a number of irreversible reactions [1]. Overproduction and accumulation of AGEs having a key role in aging has been shown to result in several structural and functional disorders [2, 3]. Production of AGEs depends on the blood glucose concentration and the exposure time and may result directly from the hyperglycemia [4]. Advanced glycation end-products cross-link with tissue proteins, lipids, and DNA and result in a number of biochemical changes.
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