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

The beta adrenergic (//AR) 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 ab- dominal 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//1-antagoifist or isoproterenol or carba- chol allowed the determination of the two//AR subtypes and of the low and high affinity sites (defined by the inhibitory constant Ki) for both//IAR and MR. In LVH, receptor density decreased for each of total//AR,//1AR subtype, high affinity (Ki 6-8 nM) //1AR sites (from 26 _+ 2 to 19 + 3 fmol/mg protein, P < 0.05), total MR and high affinity (Kj 12 nM) MR sites (from 63 + 6 to 40 + 4 fmol/mg protein, P < 0.001). The//AR and MR densities dropped in parallel so that the MR///AR ratio remained unchanged. In sharp contrast (because the LVs were bigger) the quantities of total//AR,//1AR subtype, //IAR 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 un- changed, suggesting that either both synthesis and degra- dation were augmented in parallel or that during the pro- cess 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 modi- fied beyond the level of the receptors.