Involvement of altered arginase activity, arginase I expression and NO production in accelerated intimal hyperplasia following cigarette smoke extract.
In the present experiments, we tried to elucidate whether changes in arginase activity, protein expression of arginase-I and -II, and NO production are involved in accelerating the intimal hyperplasia following administration of cigarette smoke extract (CSE). The intimal hyperplasia was caused by removing endothelial cells with the aid of balloon embolectomy catheter in the right carotid artery of the male rabbit. The left carotid artery underwent sham operation and served as control. CSE was prepared by bubbling a stream of cigarette smoke into phosphate buffered saline. Rabbits were given subcutaneously with CSE once a day for 5 weeks from 1 week before to 4 weeks after the surgery. The specimens were assessed histologically and the intima/media ratio (%) was evaluated as an index of the intimal hyperplasia. The accelerated intimal hyperplasia with CSE was accompanied by the augmentation of the impaired cyclic GMP production, enhanced overall arginase activity and up-regulation of arginase-I. Pearson's correlation coefficient analyses revealed the close relationships among the arginase activities in endothelial cells and smooth muscle layer, the intimal/media ratio and cyclic GMP production. These results suggest that the enhanced arginase activity together with facilitated up-regulation of arginase-I with CSE, which was associated with the augmented impairment of NO production, shed a new light on the processes associated with accelerating the intimal hyperplasia in rabbit carotid arteries following CSE.
Nagai
Akiko
A
Department of Inorganic Materials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.
Imamura
Masatoshi
M
Watanabe
Takayasu
T
Azuma
Hiroshi
H
D000818:Animals; D001119:Arginase / Q000378:metabolism*; D015153:Blotting, Western; D002339:Carotid Arteries; D006152:Cyclic GMP / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry*; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D012906:Smoke; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001119:Arginase; D006152:Cyclic GMP