Time course of action of amlodipine and felodipine in the rat is most rapid in small arteries.
The time course of action of amlodipine was compared to that of felodipine in rat mesenteric resistance arteries and aorta. Both amlodipine and felodipine caused a concentration-dependent relaxation of K(+)-depolarized resistance arteries: with amlodipine 3 x 10(-8) M and felodipine 10(-9) M, complete relaxation was reached after 40 min and 10 min, respectively. Furthermore, in resistance arteries, the time course of action of both drugs was shortest in vessels with the smallest diameter. In aorta, both drugs caused a marked relaxation of K(+)-induced tone, without reaching a maximal effect within 2 h. Recovery of K(+)-induced tone after both drugs was complete in resistance arteries, but not aorta, within 2 h. In resistance arteries exposed to K+ depolarization or noradrenaline, both drugs displayed the characteristics of 1,4-dihydropyridine Ca2+ channel antagonists. The results show that amlodipine was slower to have an effect than felodipine, but that both drugs acted fastest in the smallest arteries.
Videbaek
L M
LM
Institute of Pharmacology, University of Aarhus, Denmark.
Kvist
S
S
Mulvany
M J
MJ
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015736:Felodipine / Q000008:administration & dosage / Q000494:pharmacology*; D016014:Linear Models; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D017311:Amlodipine; D015736:Felodipine; D011188:Potassium; D002118:Calcium