Julou G, Freslon J L
Eur J Pharmacol. 1986 Oct 7;129(3):261-70. doi: 10.1016/0014-2999(86)90436-x.
The effects of four calcium entry blockers (CEBs), diltiazem (D), verapamil (V), nifedipine (NF) and nicardipine (NC), were investigated on Ca2+ concentration-effect curves of rat depolarized (K+, 40 mM) or noradrenaline (NA, 3 microM)-exposed mesenteric resistance vessels. Under control conditions, NA-exposed vessels were more sensitive to Ca2+ (pD2: 4.12 +/- 0.11) than depolarized vessels (pD2: 3.16 +/- 0.02, P less than 0.01) whereas the maximal active wall tensions were not significantly different (2.86 +/- 0.11 mN/mm and 2.11 +/- 0.34 mN/mm respectively). In depolarized vessels, D, V, NF and NC induced a concentration-dependent shift to the right and a depression of the maximal effect of the Ca2+ curves, which suggested a non-competitive antagonism. The IC50 (concentration of CEB producing a 50% inhibition of the maximal contractile response from control curve) values were: D: 3 X 10(-7), V: 1.3 X 10(-7), NF: 4.5 X 10(-9), NC: 3 X 10(-9) M. In NA-exposed vessels, the CEBs produced a concentration-dependent shift to the right of the Ca2+ curves before depressing their maximal effect. This suggested that the antagonism was different from that observed in depolarized arteries. In this case, the IC50 values were: D: 4.5 X 10(-7), V: 2 X 10(-7), NF: 9 X 10(-9), NC: 7 X 10(-9) M. Although the gating mechanisms activated in this study were differently affected by CEBs, since there were marked qualitative differences in their antagonistic effects on Ca2+ concentration-effect curves, depolarization and NA promoted the entry of Ca2+ into smooth muscle cells of rat resistance vessels by mechanisms with the same sensitivity to CEBs as expressed by IC50 values.
