Effects of calcium channel blocker azelnidipine on experimental abdominal aortic aneurysms.
OBJECTIVE
Azelnidipine has recently been recognized in vascular remodeling. However, the effects of azelnidipine on aneurysmal disease have not yet been studied. The aim of this study was to evaluate whether azelnidipine can inhibit a further expansion of aneurysmal disease.


METHODS
Experimental abdominal aortic aneurysms (AAAs) were created in a rat model by perfusing elastase. The rats in the first group received no treatment (n=10). In the second group (n=10) azelnidipine (2 mg/kg) was administered to the animals from 3 days before perfusion. The aortic diameter (AD) was measured at the time of initial surgery and death on postoperative day 14. The production of matrix metalloproteinases (MMP)-2 and -9 was analyzed by gelatin zymography.


RESULTS
The aortic diameter was smaller in the azelnidipine group than in the control (7.875+/-1.454 vs 10.745+/-0.551 mm, P<0.01). the active MMP-2 and MMP-9 levels decreased in the azelnidipine group. Hematoxylin-eosin and elastin staining revealed fewer changes in the inflammatory infiltrate and degradation of elastin in the azelnidipine group.


CONCLUSIONS
Azelnidipine reduced the expansion of experimental AAAs. Azelnidipine therefore appears to influence the inflammatory oxidative response seen in AAAs while also decreasing the MMP-2 and MMP-9 levels. In addition, azelnidipine inhibited aortic dilatation.
Yokokura
Hiroko
H
Department of Surgery, Kurume University of Medicine, 67 Asahimachi, Kurume-shi, Fukuoka, 830-0011, Japan.
Hiromatsu
Shinichi
S
Akashi
Hidetoshi
H
Kato
Seiya
S
Aoyagi
Shigeaki
S
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects*; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001383:Azetidinecarboxylic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C061679:azelnidipine