Action of calcium antagonists and agonists on isolated human thoracic arteries used for coronary artery bypass grafting.
BACKGROUND
The goal of this study was to investigate the modulation of the contraction-relaxation effects in isolated human thoracic artery samples of three calcium-channel antagonists, amlodipine (CAS [88150-42-9]), cerebrocrast (CAS [118790-71-9]) and diltiazem (CAS [42399-41-7]), and two calcium-channel agonists, CGP 28392 (CAS [89289-93-0]) and benzimidazole derivative. To estimate the endothelial function of the artery samples, carbachol, an agonist of muscarinic receptors, was used.


METHODS
The experiments were conducted on isolated human thoracic artery samples, and their isometric contractions were recorded using an i-FOT10 force transducer. Cumulative concentration-contraction curves of the tested agents (10(-7) to 10(-4) M) were established.


RESULTS
Carbachol at concentrations of 10(-7) to 10(-6) M did not cause any relaxation of artery rings precontracted by 10(-4) M phenylephrine, and at concentrations of 10(-5) and 10(-4) M, isometric contractions increased by 7% and 20%, respectively. In response to amlodipine, cerebrocrast and CGP28392, the contraction of artery samples increased significantly, whereas diltiazem and benzimidazole derivative caused their relaxation by ≈55%.


CONCLUSIONS
The obtained data indicate that the endothelium of the thoracic artery, which is used for coronary artery bypass grafting, is damaged by and may have some influence on the inadequate response of 1,4-dihydropyrine type calcium-channel antagonists.
Institute of Cardiology at the Medical Academy of the Lithuanian University of Health Sciences, Kaunas Sukileliu 17, Kaunas, LT-50009, Lithuania. vidag24@gmail.com
Vida
V
Garaliene
Vygantas
V
Barsys
Povilas
P
Jakuška
Rimantas
R
Benetis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D001026:Coronary Artery Bypass / Q000379:methods; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D013895:Thoracic Arteries / Q000187:drug effects* / Q000378:metabolism
D001562:Benzimidazoles; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011725:Pyridines; C073838:2,6-dimethyl-3,5-bis(2'-propoxyethoxycarbonyl)-4-(2''-difluoromethoxyphenyl)-1,4-dihydropyridine; D017311:Amlodipine; C040525:CGP 28392; D002217:Carbachol; D004110:Diltiazem