In the present study, we aimed to examine the effect of blockade of L-type Ca2+ channels (LTCC) and in addition the removal of extracellular Ca2+, on EFS-induced relaxations in rings of rat mesenteric artery. EFS applied to the tissues precontracted with phenylephrine caused relaxations which were markedly inhibited by nifedipine (10(-7) M) and tetraethylammonium (TEA) (1 mM). Addition of LTCC opener BAY K 8644 (10(-7) M) failed to enhance the relaxations. Upon removal of Ca2+, EFS with the same stimulation parameters produced frequency-dependent transient contractions. Tetrodotoxin (10(-6) M), capsaicin (10(-5) M) and removal of endothelium did not alter these contractions suggesting that they were not neural in origin and endothelium-derived contracting factors were unlikely to be involved. However, they were increased by nearly 40% in response to BAY K 8644 (10(-7) M) and were inhibited by nifedipine (10(-7) M), indicating that activation of the LTCCs was essential. Inositol triphosphate (InsP(3)) receptor antagonist 2-APB (10(-4) M) significantly reduced, and high concentration of caffeine (20 mM) almost totally suppressed the contractions. These results suggest that in the absence of extracellular Ca2+ EFS through membrane depolarization, evokes the opening of the LTCCs which subsequently leads to the release of Ca2+ from internal stores via InsP(3) receptors, a phenomenon known as Ca2+ channel-induced Ca2+ release (CCICR), to trigger vasoconstriction. That activation of LTCCs causes arterial relaxation or contraction depending on the Ca2+ status apparently exemplifies how the same messenger fulfils opposing physiological functions in a given cell. (C) 2013 Elsevier Ltd. All rights reserved.