title: Compared effects of calcium entry blockers on calcium-induced tension in rat isolated cerebral and peripheral resistance vessels.
abstract: The effects of the calcium entry blockers verapamil (V), diltiazem (D), nifedipine (NF) and nicardipine (NC) have been studied on calcium concentration-effect curves elicited in depolarized (K+, 40 mmol/l) and in serotonin-exposed (6 mumol/l) rat middle cerebral arteries (RMCA) in order to compare the relative potencies of the blockers against these two calcium channel activating mechanisms. In control conditions, Ca2+ sensitivity expressed as pD2 and maximal active wall tension (AWT) were not significantly different in depolarized and in 5-HT-exposed vessels: pD2: 3.39 +/- 0.08 vs 3.50 +/- 0.06 and AWT: 0.93 +/- 0.15 mN.mm-1 vs 0.90 +/- 0.16 mN.mm-1 respectively. V, D, NF and NC displaced Ca2+ control curves to the right and depressed the maximum contractile response in the two experimental conditions, which suggests a noncompetitive type of antagonism. All the blockers were more potent inhibitors of Ca2+-induced contractions in depolarized than in serotonin-exposed middle cerebral arteries. The IC50 values (concentration of blockers producing a 50% inhibition of maximal control contractile response) were (nmol/l): V = 20, D = 120, NF = 0.4, NC = 1 and V = 400, D = 10,000, NF = 20, NC = 7 in depolarized and serotonin-exposed arteries respectively. From these IC50 values, the relative order of potency of the CEB's was not the same in the two experimental conditions suggesting that while serotonin and K+ both promote the entry of Ca2+ into vascular smooth muscle cells of RMCA, they either activate a different gating mechanism associated with a single common channel or perhaps distinct channels.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Université Louis Pasteur, Laboratoire de Pharmacodynamie (CNRS UA 600), Strasbourg, France.
authors.forename: G
authors.initials: G
authors.lastname: Julou-Schaeffer
authors.forename: J L
authors.initials: JL
authors.lastname: Freslon
mesh_terms: D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D012701:Serotonin; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium