NH4CL-INDUCED CONTRACTION OF PORCINE CORONARY-ARTERY INVOLVES ACTIVATION OF DIHYDROPYRIDINE-SENSITIVE CA2+ ENTRY

The role of voltage-dependent, dihydropyridine-sensitive Ca2+ channels in NH4Cl-induced vasoconstriction was investigated in isolated porcin e coronary arteries by measuring in parallel isometric tone and Ca-45( 2+) uptake. NH4Cl (10-80 mM) concentration dependently induced tonic c ontractions which were preceded by a time lag of several minutes. Cont ractile responses to high (60 mM) as well as low (25 mM) concentration s of NH4Cl were markedly inhibited by 1 mu M nifedipine or removal of extracellular Ca2+. The contractile effect of 25 mM NH4Cl was substant ially enhanced by increasing extracellular K+ to 14.7 mM or by pretrea tment of coronary arteries with either 5 mM tetraethylammonium chlorid e or 0.1 mu M -5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carbo xylic acid methyl ester (BAY K8644). NH4Cl (60 mM) significantly incre ased Ca-45(2+) uptake with a lag time of more than 5 min. The increase in Ca-45(2+) uptake induced by 60 mM NH4Cl was abolished in the prese nce of 1 mu M nifedipine. Although NH4Cl (25 mM) did not detectably st imulate Ca-45(2+) uptake in normal K+ solution, it significantly augme nted Ca-45(2+) uptake when extracellular K+ was increased to 14.7 mM. Furthermore, NH4Cl (20 mM) potentiated histamine-induced contraction o f coronary arteries. This potentiating effect of NH4Cl was completely antagonized by nifedipine. Our results suggest an involvement of nifed ipine-sensitive Ca2+ channels in NH4Cl-induced vasoconstriction of por cine coronary artery.