Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit.
1. Intimal thickening is a common site for atherosclerosis. Therefore, we investigated whether the calcium entry blocker verapamil (10 mg kg-1 body weight day-1, s.c.) can retard intimal thickening and changes in vascular reactivity induced by a non-occlusive, silicone collar positioned around the left carotid artery of rabbits. The contralateral carotid artery was sham-operated and served as a control. 2. Verapamil and placebo (saline 0.1 ml kg-1, day-1, s.c.) treatments were initiated 7 days before placing the collar and lasted 3 weeks. Thereafter, segments were cut from collared and sham-treated arteries for histology and isometric tension recording. 3. The intima/media (I/M ratio increased after 14 days of collar treatment, but intimal thickening was not inhibited by verapamil (I/M ratio placebo 0.31 +/- 0.07, verapamil 0.32 +/- 0.09). 4. The collar decreased the capacity to develop force, as indicated by the response to a supramaximal concentration of KCl, decreased the sensitivity (pD2) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5-hydroxytryamine (5-HT). 5. Although verapamil did not affect intimal thickening, it normalized the hypersensitivity to 5-HT in collared arteries. 6. The contraction to the supramaximal concentration of KCl was not affected by verapamil. Verapamil decreased the Emax of ACh, but this was only seen in collar-treated arteries. Verapamil also decreased the sensitivity to ACh and Phe, in both sham- and collar-treated arteries. 7. We conclude that verapamil, without preventing thickening of the intima, can modify collar-induced changes in vascular reactivity.
Ustünes
L
L
Department of Parmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey.
Yasa
M
M
Kerry
Z
Z
Ozdemir
N
N
Berkan
T
T
Erhan
Y
Y
Ozer
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D010656:Phenylephrine; D012701:Serotonin; D011189:Potassium Chloride; D014700:Verapamil; D000109:Acetylcholine