Diverse effects of calcium channel blockers in the collar model.
OBJECTIVE
Calcium channel blockers (CCBs) are among the most frequently prescribed cardiovascular drugs. It has been shown that these drugs have antiatherosclerotic effects in both experimental and clinical settings. However, calcium channel blockers have markedly different chemical structures and different effects on the cardiovascular system. We investigated the effect of CD-832, a Ca(+2) channel antagonist, on collar-induced intimal thickening, as well as accompanied reactivity changes in rabbit carotid artery.


RESULTS
Rabbits received 5 mg/kg/day CD-832 or vehicle (polyethylene glycol, 0.5 ml/kg/day) intramuscularly for a week before and 2 weeks after the collar application. Histological and isometric force measurements were performed in segments from sham and collared carotid arteries. A three-week treatment with CD-832 did not inhibit the intimal thickening caused by perivascular application of a silicone collar. Potassium chloride (KCl), phenylephrine, 5-hydroxytryptamine (5-HT, serotonin) and histamine induced concentration-dependent contractions in both sham-operated (sham) and collared arteries. Collar-induced attenuations in maximum KCl, histamine, phenylephrine and 5-HT contractions were not affected by CD-832. Collaring caused an increase in pD2 values of 5-HT and a decrease in those of phenylephrine, histamine and acetylcholine. CD-832 did not affect the altered sensitivity to these agonists.


CONCLUSIONS
These results demonstrate that, in rabbit carotid artery, CD-832 did not inhibit the collar-induced intimal thickening and did not affect the accompanying changes in vascular reactivity.
Kerry
Zeliha
Z
Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, Izimir, Turkey. Kerryz@pharmacy.ege.edu.tr
Yasa
Mukadder
M
Sevin
Gülnur
G
Reel
Buket
B
Yetik Anacak
Günay
G
Ozer
Asli
A
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D018494:Histamine Agents / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D008955:Models, Cardiovascular; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; C082828:CD 832; D002121:Calcium Channel Blockers; D018494:Histamine Agents; D018490:Serotonin Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009536:Niacinamide; D012701:Serotonin; D011189:Potassium Chloride; D009543:Nifedipine; D000109:Acetylcholine