Influence of stimulation interval on inotropism mediated by alpha-adrenoceptors in the left atria of rabbits.

The inotropic effects induced by alpha-adrenoceptor stimulation were investigated in the left atria of rabbits at various stimulation rates and were compared with those by beta-adrenoceptor stimulation. Phenylephrine at a concentration of 10(-5) M in the presence of 5 X 10(-5) M sotalol more increased the contractile force with decreasing the rate of stimulation from 120 to 30 beats/min, whereas the same procedure resulted in a negative inotropic effect at low stimulation rates such as 1 beat/min. Inversion from the positive inotropism to the negative one was observed to occur in a range of 3 to 12 beats/min. Rested state contractions obtained by a stimulation rate of 1 beat per 5 min, i.e. a rest period of 300 sec, were significantly decreased by phenylephrine, while increased by 5 X 10(-9) M isoproterenol. This depressive effect of phenylephrine was antagonized by 3 X 10(-6) M phentolamine. Post rest contractions (PRC) which were elicited following a rest period of 300 sec after steady stimulation of 60 beats/min, were inconsistently affected by phenylephrine in contrast with the consistent and significant increase by isoproterenol. Of 17 preparations treated with phenylephrine, 9 showed an increase and others a decrease in PRC. However, reduction of NaCl concentration by 50% resulted in a decrease in PRC in all preparations treated with phenylephrine without affecting the increase produced by isoproterenol. These results indicate that alpha-adrenoceptor-mediated positive inotropic effect inverts to a negative one when the contractions have a long interval of rest.