Histamine Increases Vascular Tone and Intracellular Calcium Level Using Both Intracellular and Extracellular Calcium in Porcine Coronary Arteries

Abstract

Effects of histamine on the tone and intracellular calcium level (Ca²⁺_i) in porcine coronary arteries were simultaneously investigated by use of the fura-2 microscopic fluorometric method. Histamine (10^-6-10^-4 M) induced concentration-dependent increases in tone and Ca²⁺_i, but these responses were not sustained. Histamine induced a larger contraction than did KCI with a similar increase in Ca²⁺_i. Depletion of the caffeine-sensitive Ca²⁺ store with ryanodine (3×10^-5 M) and repetitive applications of caffeine (2.5×10^-2 M) scarcely affected contractile and Ca²⁺_i responses to histamine. In Ca²⁺-free medium or in the presence of verapamil (10^-6 M), histamine produced a briefer increase in Ca²⁺_i and a smaller contraction than in normal medium. When histamine or caffeine was repetitively applied in Ca²⁺-tree medium, the first application produced an increase in Ca²⁺_i but the second application produced no increase. Although caffeine increased Ca²⁺_i after repetitive histamine applications, histamine failed to increase Ca²⁺_i after repetitive caffeine applications in Ca²⁺_i-free medium. These results indicate that vascular contraction induced by histamine may involve the following mechanisms: an increase in Ca²⁺ influx through Ca²⁺ channels, release of Ca2+ from the intracellular Ca²⁺ store which has an interaction with the caffeinesensitive Ca²⁺ store, and sensitization of contractile proteins to Ca²⁺.