Beta adrenergic and muscarinic receptors in compensatory cardiac hypertrophy of the adult rat

Abstract

The beta adrenergic (βAR) and muscarinic (MR) receptors have been quantitated in parallel, using ¹²⁵I-pindolol and ³H-quinuclidinylbenzilate, in a model of compensatory left ventricular (LV) hypertrophy (LVH), which developed in rats 4–6 weeks after an abdominal aortic stenosis. Since aortic banding resulted in a pronounced LVH of 62%, the results were expressed both in terms of density (fmol/mg protein) and quantity (fmol per LV). In addition, competition curves using either a specific β1-antagonist or isoproterenol or carbachol allowed the determination of the two βAR subtypes and of the low and high affinity sites (defined by the inhibitory constant K _i) for both β1AR and MR. In LVH, receptor density decreased for each of total βAR, β1AR subtype, high affinity (K _i 6–8nM) β1AR sites (from 26±2 to 19±3 fmol/mg protein, P<0.05), total MR and high affinity (K _i 12 nM) MR sites (from 63±6 to 40±4 fmol/mg protein, P<0.001). The βAR and MR densities dropped in parallel so that the MR/βAR ratio remained unchanged. In sharp contrast (because the LVs were bigger) the quantities of total βAR, β1 AR subtype, β1AR high affinity sites, total MR and MR high affinity sites per LV were unmodified. Thus, in compensatory LVH the total quantity of receptors per LV was unchanged, suggesting that either both synthesis and degradation were augmented in parallel or that during the process of cardiac hypertrophy they are not regulated, i. e., that the genes encoding for the two receptors were not activated, as it has been suggested for other membrane proteins. Assuming that the high affinity sites represent the receptors coupled to the adenylyl cyclase, we also propose that the overall regulatory systems were modified beyond the level of the receptors.