Calcium channel blocking properties of amlodipine in vascular smooth muscle and cardiac muscle in vitro: evidence for voltage modulation of vascular dihydropyridine receptors
| Autor: | R A, Burges, D G, Gardiner, M, Gwilt, A J, Higgins, K J, Blackburn, S F, Campbell, P E, Cross, J K, Stubbs |
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| Rok vydání: | 1987 |
| Předmět: |
Male
Dose-Response Relationship Drug Nifedipine Guinea Pigs Action Potentials Heart Rats Inbred Strains In Vitro Techniques Receptors Nicotinic Calcium Channel Blockers Myocardial Contraction Muscle Smooth Vascular Rats Electrophysiology Kinetics Heart Rate Depression Chemical Potassium Animals Calcium Amlodipine Calcium Channels |
| Zdroj: | Journal of cardiovascular pharmacology. 9(1) |
| ISSN: | 0160-2446 |
| Popis: | Amlodipine was twice as potent as nifedipine at inhibiting Ca2+-induced contractions in depolarised rat aorta (IC50 1.9 nM vs. 4.1 nM) but, unlike nifedipine, displayed a very slow onset of action. Contractions induced by depolarising steps with 45 mM K+ were much less potently blocked by amlodipine (IC50 19.4 nM), whereas the potency of nifedipine was little changed (IC50 7.1 nM). This difference may be explained by a modulated receptor hypothesis, similar to that described for cardiac muscle, in which block of vascular calcium channels by dihydropyridines is enhanced at depolarized membrane potentials, such voltage-dependence only being apparent with a slow-acting drug such as amlodipine. Recovery from amlodipine block of K+-responses in rat portal vein after drug washout was also very slow. Amlodipine and nifedipine blocked phenylephrine-induced contractions of the rat aorta with potencies similar to those against depolarisation-induced responses. Negative inotropic potencies of amlodipine and nifedipine in perfused guinea pig hearts were approximately one-tenth those against Ca2+-induced contractions in rat aorta. Amlodipine caused complete block of guinea pig papillary muscle single-cell slow action potentials at a concentration (5 microM) that had no effect on upstroke velocity of normal, fast potentials but reduced the duration of the plateau phase. |
| Databáze: | OpenAIRE |
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