Compared effects of calcium entry blockers on calcium-induced tension in rat isolated cerebral and peripheral resistance vessels.
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)
Julou-Schaeffer
G
G
Université Louis Pasteur, Laboratoire de Pharmacodynamie (CNRS UA 600), Strasbourg, France.
Freslon
J L
JL
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
D002121:Calcium Channel Blockers; D012701:Serotonin; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium