Effect of Ni2+ on the multiphasic positive inotropic responses to histamine mediated by H1-receptors in left atria of guinea pigs.
Effects of calcium antagonists and Ni2+ on the positive inotropic responses to histamine mediated by H1-receptors were investigated in left atria of guinea pigs. The preparations were electrically driven at 0.5 Hz in Krebs-Henseleit solution at a temperature of 30 degrees C unless stated otherwise. Histamine in low concentrations of 10 and 100 nmol/1 produced a monophasic positive inotropic effect, whereas in concentrations higher than 1 mumol/1 it exerted a multiphasic inotropic response composed of an initial increasing phase (initial component) and a second and late developing, greater positive inotropic phase (second component). These two components were sometimes separated by a transient decrease in developed tension. Both positive inotropic components caused by 3 mumol/1 histamine were inhibited by the H1-antagonists mepyramine, D-chlorpheniramine and diphenhydramine in a concentration-dependent manner, but not by the H2-antagonist cimetidine. Pretreatment with Ni2+ in concentrations of 0.2 and 0.5 mmol/1 preferentially suppressed the second component of the inotropic effect produced by 3 mumol/1 histamine without significantly affecting the initial component. On the other hand, the monophasic positive inotropic effect of 30 nmol/1 histamine was almost unaffected by this cation. The concentration-response curves for the positive inotropic effect of histamine were hardly influenced by Ni2+ in the range of lower concentrations of histamine, but significantly suppressed in the range of higher concentrations of the agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology*; D011968:Receptors, Histamine / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D002395:Catecholamines; D006633:Histamine Antagonists; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D009532:Nickel; D006632:Histamine; D012110:Reserpine