Pravastatin restores DDAH activity and endothelium-dependent relaxation of rat aorta after exposure to glycated protein.
This study was designed to investigate whether glycated bovine serum albumin (AGE-BSA) inhibits dimethylarginine dimethylaminohydrolase (DDAH) activity to contribute to its adverse effect on endothelium-dependent relaxation in rat aorta, and whether pravastatin reverses the inhibition of DDAH activity and endothelial dysfunction induced by AGE-BSA. Endothelium-dependent relaxation of aortic rings was measured by isometric tension recording, and DDAH activity, and the contents of nitrite/nitrate as well as malondialdehyde (MDA) in aortic tissue were determined after exposure of Sprague-Dawley rat aorta to AGE-BSA (1.70 mmol/L) for 60 minutes in the presence or absence of pravastatin. In comparison with control, both endothelium-dependent relaxation and DDAH activity (0.032 +/- 0.002 versus 0.095 +/- 0.003 U/g protein, n = 5, P < 0.01) were significantly inhibited in isolated rat aorta after exposure to AGE-BSA, which was accompanied by decreases of nitrite/nitrate contents and elevations of MDA levels in aorta. Treatment with pravastatin (1 mmol/L) not only prevented the inhibition of endothelial function but also reversed the decrease of DDAH activity induced by AGE-BSA and normalized the alterations in nitrite/nitrate and MDA contents. Similar effects were observed when rat aorta exposed to AGE-BSA in the presence of antioxidant pyrrolidine dithiocharbamate (PDTC, 30 micromol/L) or protein kinase C inhibitor chelerythrine (1 micromol/L). These results suggested that decreased DDAH activity may be involved in endothelial dysfunction of rat aorta induced by AGE-BSA, and that pravastatin restores DDAH activity and endothelium-dependent relaxation after aorta exposure to AGE-BSA, which may be secondary to its antioxidative effects.
Yin
Qing-Feng
QF
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Hunan, P. R. China.
Xiong
Yan
Y
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D017127:Glycation End Products, Advanced; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D000581:Amidohydrolases; C059999:dimethylargininase; D017035:Pravastatin