Enhanced noradrenaline response in cardiomyopathic hamsters: possible relation to changes in adrenoceptors studied by radioligand binding

Abstract

To assess the possible relation between catecholamine responses and adrenoceptor affinity and density, we compared the effect of noradrenaline, isoprenaline and ouabain on right ventricular muscle strips from normal and cardiomyopathic hamsters with α₁₋ and β-adrenoceptor characteristics assessed by radioligand binding methods. At concentrations of 1.28, 2.56, 5.0 and 10 × 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 increases of 65 ± 8, 92 ± 8, 109 ± 9 and 115 ± 10% occurred in cardiomyopathic hamsters (n = 11, all P < 0.02). The responses to isoprenaline (E_maK = 82%) and ouabain did not differ between the two groups of hamsters. [³H]-prazosin, a new radioligand, and [−³H]-dihydroalprenolol were used to assess α₁₋ and β-adrenoceptors in cardiac membranes. By Scatchard analysis, the K_D 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]-dihydroal-prenolol (both P < 0.05). Histochemically, oxidative and glycolytic activity were normal but lyso-zosomal acid phosphatase was high. Possible explanations for the raised response to noradrenaline in cardiomyopathic hamsters include an increased concentration of noradrenaline in the synaptic cleft due to defective neuronal uptake and / or stimulation of an augmented population of α₁-(postsynaptic) adrenoceptors.