NH 4Cl-induced contraction of porcine coronary artery involves activation of dihydropyridine-sensitive Ca 2+ entry

Abstract

The role of voltage-dependent, dihydropyridine-sensitive Ca 2+ channels in NH 4Cl-induced vasoconstriction was investigated in isolated porcine coronary arteries by measuring in parallel isometric tone and 45Ca 2+ uptake. NH 4Cl (10–80 mM) concentration dependently induced tonic contractions which were preceded by a time lag of several minutes. Contractile responses to high (60 mM) as well as low (25 mM) concentrations of NH 4Cl were markedly inhibited by 1 μM nifedipine or removal of extracellular Ca 2+. The contractile effect of 25 mM NH 4Cl was substantially enhanced by increasing extracellular K + to 14.7 mM or by pretreatment of coronary arteries with either 5 mM tetraethylammonium chloride or 0.1 μM 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester (BAY K8644). NH 4Cl (60 mM) significantly increased 45Ca 2+ uptake with a lag time of more than 5 min. The increase in 45Ca 2+ uptake induced by 60 mM NH 4Cl was abolished in the presence of 1 μM nifedipine. Although NH 4Cl (25 mM) did not detectably stimulate 45Ca 2+ uptake in normal K + solution, it significantly augmented 45Ca 2+ uptake when extracellular K + was increased to 14.7 mM. Furthermore, NH 4Cl (20 mM) potentiated histamine-induced contraction of coronary arteries. This potentiating effect of NH 4Cl was completely antagonized by nifedipine. Our results suggest an involvement of nifedipine-sensitive Ca 2+ channels in NH 4Cl-induced vasoconstriction of porcine coronary artery.