The effect of (±)-4-NO 2 -propranolol, (±)-7-NO 2 -propranolol, and (±)- propranolol on the rat isolated right atrium

Abstract

Abstract 6-Nitrodopamine (6-ND) is released from rat isolated atria and has positive chronotropic action, which is selectively blocked by β1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here the effects of (±)-propranolol, (±)-4-NO2-propranolol, and (±)-7-NO2-propranolol, were investigated in the rat isolated right atrium. The atrium was mounted in gassed (95%O2:5%CO2), heated (37°C) glass chambers, containing Krebs-Henseleit’s solution. Tissues were allowed to equilibrate under a resting tension of 10mN for 1 hour, and the isometric tension was registered using a PowerLab system. (±)-propranolol, (±)-4-NO2-propranolol and (±)-7-NO2-propranolol, caused concentration-dependent falls in the spontaneous atrial frequency (pEC50 were 4.80 ± 0.10, 4.64 ± 0.10, and 4.95 ± 0.10, respectively). Noradrenaline (1nM–30µM), and adrenaline (1nM–100µM), caused concentration-dependent increases in atrial rate. The calculated pA2 values for (±)-propranolol, (±)-4-NO2-propranolol, and (±)-7-NO2-propranol obtained for noradrenaline-induced positive chronotropic effects were 8.21 ± 0.35, 6.41 ± 0.21, and 8.35 ± 0.35, respectively. The positive chronotropic effect induced by 6-ND (10pM) was blocked by (±)-propranolol (1µM), and (±)-4-NO2-propranolol (30nM). (±)-7-NO2-propranol (1µM) had no effect on 6-ND (10pM)-induced increases in atrial rate. The pEC50 of (±)-propranolol, (±)-4-NO2-propranolol and (±)-7-NO2-propranolol were significantly shifted to the right in L-NAME treated atria. The discrepancy between pA2 values of (±)-propranolol and its respective pEC50 indicates that the falls in atrial rate induced by (±)-propranolol should not be attributed to b-adrenergic antagonism. The finding that (±)-4-NO2-propranolol causes falls in spontaneous atrial rate only in concentrations that affect 6-ND positive chronotropic effect, confirms the role of this catecholamine as endogenous modulator of heart chronotropism.