Compared effects of calcium entry blockers on calcium-induced tension in rat isolated cerebral and peripheral resistance vessels

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1987-12, Vol.336 (6), p.670-676
• Main Authors: JULOU-SCHAEFFER, F, FRESLON, J. L
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - antagonists & inhibitors; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Cardiovascular system; Cerebral Arteries - drug effects; Diltiazem - pharmacology; Female; In Vitro Techniques; Medical sciences; Nicardipine - pharmacology; Nifedipine - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Serotonin - pharmacology; Vascular Resistance - drug effects; Vascular wall; Verapamil - pharmacology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00165759

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.