Enhanced noradrenaline response in cardiomyopathic hamsters: possible relation to changes in adrenoceptors studied by radioligand binding.
To assess the possible relation between catecholamine responses and adrenoceptor affinity and density, we compared the effect of noradrenaline, isoprenaline and ouabain on the right ventricular muscle strips from normal and cardiomyopathic hamsters with alpha 1- and beta-adrenoceptor characteristics assessed by radioligand binding methods. At concentrations of 1.28, 2.56, 5.0 and 10 x 10 (-6) mol . litre (-1) noradrenaline raised isometric tension by 27 +/- 4, 39 +/- 5, 52 +/- 5 and 61 +/-6% in normal animals (n = 6). Corresponding increase of 65 +/- 8, 92 +/- 8, 109 +/- 9 and 115 +/- 10% occurred in cardiomyopathic hamsters (n=11, all P less than 0.02). The responses to isoprenaline (Emax =82%) and ouabain did not differ between the two groups of hamsters. [3H]-prazosin, a new radioligand, and [-3H]-dihydroalprenolol were used to assess alpha 1- and beta-adrenoceptors in cardiac membranes. By Scatchard analysis, the KD values for both ligands did not differ between normal and cardiomyopathic hamsters, but the maximum number of binding sites was higher in the myopathic group: 5.5 vs 3.9 fmol . mg [-1] protein for [3H]-prazosin and 27 vs 20 fmol . mg [-1] protein for [-3H]-dihydroalprenolol (both P less than 0.05). Histochemically, oxidative and glycolytic activity were normal but lysosomal acid phosphatase was high. Possible explanations for the raise response to noradrenaline in cardiomyopathic hamster include and increased concentration of noradrenaline in the synaptic cleft due to defective neuronal uptake and / or stimulation of an augmented population of alpha 1-(postsynaptic) adrenoceptors.