Contractile responses to calcium chloride in rat aortic rings bathed in K+-free solution are resistant to organic calcium antagonists.
1. In rat aortic rings, devoid of functional endothelium, suspended in a modified Krebs solution (KCl: 0 mM; CaCl2: 0.63 mM), addition of CaCl2 (0.89-10 mM) produced concentration-related increases in tension (Emax = 2.38 +/- 0.10 g, EC50 = 2.31 +/- 0.15 mM, n = 36). 2. The Ca2+ evoked contractile responses were not modified by cinnarizine (10 microM), diltiazem (1 microM), ryanodine (10 microM), verapamil (1 microM), or the dihydropyridines, nitrendipine (1 microM) and (-)-Bay K 8644 (0.003-0.3 microM). 3. Cobalt chloride (0.1-1 mM) competitively antagonized the Ca2+ concentration-response curve; the Schild plot (slope 1.08 +/- 0.04), gave a pA2 value of 3.3 +/- 0.01 (n = 27). Nickel chloride (0.5-1 mM) displaced the Ca2+ concentration-response curve to the right, without an effect on the maximum response. Cadmium chloride (3-30 microM) depressed the maxima of concentration-response curves to Ca2+ with an IC50 of 15.5 +/- 1.1 microM (n = 6). 4. Monochlorobenzamil (100 microM), a Na+-Ca2+ exchange inhibitor, failed to modify the Ca2+-induced contractions. 5. In conclusion, Ca2+ evoked concentration-related contractile responses of rat aortic rings bathed in a K+-free medium; these effects were attenuated by the divalent cations cobalt, nickel and cadmium, but not modified by several organic calcium antagonists. The lack of effect of diltiazem verapamil and the dihydropyridines would suggest that, under these experimental conditions, extracellular Ca2+ enters the cytosol via pathways which are distinct from the slow (L-type) calcium channels.
Lawson
K
K
Rhone-Poulenc Sante, Centre de Recherche de Vitry, France.
Cavero
I
I
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D002122:Calcium Chloride; D011188:Potassium