Section of biological sciences Royal Academy of Medicine in Ireland

Isolated rats' hearts were perfused according to the Langendorff technique with a solution containing (gm./litre) NaC1 7-6 ; NaHCO S 2.1 ; KCI 0.42 ; I~IaHPO4 0.286 ; CaCl~ 0-12 ; dextrose 2.0 and sucrose 4.5 and equilibrated to pI~ 7.25  0" 05 by aerating with 95 ~/o oxyger~ and 5 ~ carbon dioxide. The strength of contraction was recorded using a spring loaded lever and heart rate usir~g an impulse counter. In seven experiments, noradrer~line was perfused in consecutive doses of 0.01, 0.1 and 1.0 ug/ml, for 30 see. each. This caused an average increase in strength of contraction of 32, 64 and 91 ~ respectively. Prnpranolol, I ug/ml., was then perfused for 2 mill and on the average caused ~ decrease i~ strength of contraction of 11 ~/o. Noradren~line was ~gain perfnsed in doses of 0"01, 0.1, 1"0 and 10.0 ug/ml, for 30 see. each. The average increases in strength of contraction were 0, 9, 30 and 69 ~oo respectively. Thus after proprar~olol the response to noradren~li~m 0.01, 0.1 and 1.0 ug/ml, was reduced. In five other experiments the above procedure was repeated without proprmmlol. It was fotmd that the response to consecutive doses of noradrenaline was reduced during the second administration of the 0.01, 0"1 and 1.0 ug/ml, doses. These reductions were significantly smaller than. those obtained after propranolol, suggesting that the results in the propranolol series of experiments could not be explained by tachyphylaxis. The heart rate changes followed a similar but less consistent pattern. The reductions in heart rate response after propranolol were greater than those after simple repetition of the doses of noradrenaline, but, in only one ir~stauce, that of 1.0 ug/ml, noradrea~lhxe was this difference significant. In a further five experiments the effect of another adrenerglc antagonist, phenoxybenzamine, 10 ug/ml, for 2 rain., was compared with that of propranolol, I ug/mL, on the response of the rat's heart to noradrenaline, 0.1 ug/ml. As before control experiments were carried out without propranolol and phenoxybenzamine. It was found that both rate and strength of contraction responses were significantly reduced after propranolol but not after phenoxybenzamine. It is con.eluded that propranolol but not phenoxybenzamine antagonizes the effects of noradren~line on the isolatect rat's heart. Since the dose response curves for strength of contraction before and after propranolol were perallel, it is likely that propranolol antagonizes this effect of noradrenaline competitively. (We are grateful to Dr. R. G. Shanks of Imperial Chemical Industries Limited for supplying us with propranolol.)