Influence of glyceryl trinitrate on force of contraction and action potential of guinea-pig myocardium

Abstract

1. The inotropic effect of glyceryl trinitrate (GTN) was studied in guinea-pig papillary muscles and atrial strips by analysing the isometric contraction curve and the monophasic action potential (AP). 2. GTN, 7X10(-5)M in papillary muscles and at 1.4x10(-4)M in atrial strips. The maximum of the contractile force was reached in both preparations at 2x10(-4)M GTN. Positive inotropic effects were transitory (3--5 min) and were followed by marked negative inotropic effects. 3. In the presence of GTN, only 15 of 26 papillary muscles showed a positive inotropic response and there was a great variance in its intensity. Prior exposure of papillary muscles to a low GTN concentration, which by itself reduced force of contraction (like every single GTN application), was the prereqch by itself reduced force of contraction (like every single GTN application), was the prerequisite for the positive inotropic effect of a subsequent higher GTN concentration. In atrial strips the positive inotropic action was consistent and uniform. The maximum force of contraction in response to single applications of GTN was only about 50% of that in response to cumulatively increased GTN concentrations. 4. In the presence of 5x10(-4)M GTN, the tyramine concentration-effect curve was shifted to the left (by one log unit at the ED50 level). 5. Beta-Adrenoceptor blockade by(+/-)-propranolol (5x10(-6)M) or noradrenaline depletion by pretreatment of the animals with reserpine (5 mg/kg, 18--22 hrs prior to the experiment)prevented the positive inotropic effects of GTN in both preparations. Hence, the GTN-induced increase in contractile force is induced by the liberation of noradrenaline and an inhibitory effect on the monoamine oxidase (MAO) of sympathetic nerve endings might be involved. 6. In atrial preparations exposed to 5x10(-4)M GTN, time to peak force (tu) and relaxation time(t2) were shortened by 12% and 33%, respectively. Pretreatment of the animals with reserpine prevented the shortening og t1 and changed the shortening of t2 from 33% to 19%. 7. In papillary muscles, 5x10(-4) M GTN shortened t1 by 10%, while t2 was prolonged by 17% in noradrenaline-depleted, and by 36% in control muscles. Prolongation of t2 at 5x10(-4)M GTN was accompanied by an increase in the duration of the monophasic action patential (AP) in reserpine-pretreated as well as in control muscles by 12% and 26%, respectively (measured at 90% repolarization). The same GTN concentration slowed the maximum rate of depolarisiation by 32%. After 35 min the AP returned to approximately the control value. In the presence of 5x10(-4) M GTN, noradrenalin (1x10(-5)M) lengthened the AP by 38% in both, control muscles and noradrenaline-depleted preparations.