Alterations in cardiac autonomic receptors following 6-hydroxydopamine treatment in rats

To characterize the regional changes in β-adrenergic and muscarinic cholinergic receptors in rat hearts following 6-hydroxydopamine (6-OHDA) treatment, receptor binding assys, using the specific ligands [³H]dihydroalprenolol (DHA) β-adrenergic receptor) and [³H]quinuclidinyl benzilate (QNB) (muscarinic cholinergic receptor) were performed in five regions of control and treated hearts. In addition, norepinephrine (NE) concentration and choline acetyltransferase activity in hearts were assayed to characterize the model. Rats were treated with 2 x 50 mg/kg i.v. injections of 6-OHDA.HBr at 24-h intervals and the hearts were removed 1,2, and 3 weeks later. The specific [³H]DHA binding was significantly higher in the ventricles and intraventricular septum than in the right atria of control rat hearts, suggesting a regional variation for β-adrenergic receptors. Following 6-OHDA treatment, the specific [³H]DHA binding to right atria, left ventricles, and ventricular septae significantly increased compared to similar regions of control rat hearts. The B(max) value in left ventricles was significantly increased, by 32, 38, and 17%, respectively, at 1, 2, and 3 weeks without a change in the K(d), suggesting an increase in the density of β-adrenergic receptors. There was a marked (60-80%) reduction of NE levels in all regions of 6-OHDA-treated rat hearts. These results suggest a relationship between the reduction of endogenous NE and the development of the increased density of β-adrenergic receptors in the rat hearts following 6-OHDA treatment. Specific [³H]QNB binding was significantly higher in atria than in ventricles of control rat hearts. The binding to each region was unchanged at 1 and 2 weeks following 6-OHDA treatment, while it was significantly increased in most regions at 3 weeks. There was a 30% increase in the B(max) in right and left atria without a change in the K(d), suggesting a change in the receptor density. The choline acetyltransferase activity was not significantly altered in any region of 60OHDA-treated rat hearts. The present study has demonstrated that destruction of noradrenergic nerve terminals in rats with 6-OHDA leads to an increase in the density of β-adrenergic receptors and a decrease in the NE concentration and that most of the cardiac muscarinic cholinergic receptors are not located on adrenergic neurons.