| Abstract: | The positive inotropic effects of 2-pyridyl-ethylamine (PEA) and of 4-methylhistamine (4MeH) were studied in isolated guinea-pig ventricular strips electrically stimulated at a rate of 60 and 150/min. The increase in contractile tension induced by PEA (10(-7)-3 X 10(-4) M) in the presence of cimetidine (10(-5) M) was associated with a slight increase in time to peak tension and with a lengthening of the relaxation phase; the positive inotropic effect of PEA was significantly higher at a frequency of 60/min than at 150/min. Conversely, the inotropic response to 4MeH (10(-8)-3 X 10(-6) M) was not frequency dependent, and was associated with an evident decrease in relaxation time. Moreover, 4MeH consistently antagonized, in dose-dependent manner, the negative inotropic effects induced by the calcium antagonistic drug D600 and by lowering calcium concentration in the medium, and was able to restore the contractility abolished by treatment of preparations with a high K+ medium. On the other hand PEA, in the presence of cimetidine, scarcely antagonized the negative inotropic effects induced either by D600 or by low calcium solution, and was unable to restore the contractility of K+-depolarized preparations. The characteristics of the inotropic response of the H1-receptor agonist were very similar to those of the alpha-adrenoceptor agonist phenylephrine. This observation suggests that a common mechanism is probably involved in the inotropic effects mediated by H1 and by alpha receptors, and that this mechanism does not include a stimulation of the calcium transmembrane influx. |
