AUTORADIOGRAPHIC COMPARISON OF MUSCARINIC M2 AND M2 BINDING-SITES IN THE CNS OF SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS

Spontaneously hypertensive rats (SHR) respond with exaggerated presser responses of central origin in response to pharmacologic stimulation of brain muscarinic receptors when compared with those to normotensive Wistar Kyoto (WKY) rats. At least part of the enhanced response to ce ntral muscarinic stimulation may be due to alterations in the expressi on of one or more of the five subtypes of muscarinic receptors. SHR ar e also known to exhibit regional alterations in the levels of mRNA enc oding the M1, M2 and M4 receptors. Ln this study, we estimated the num ber of specific muscarinic receptor binding sites in 12-week-old SHR a nd WKY by measuring the binding of M1- and M2-selective ligands. Using standard autoradiographic techniques, coronal sections obtained from 12-week-old SHR and WKY were incubated with [H-3]pirenzepine or [H-3]A FDX 384 to label M1 and M2 receptors, respectively. Although both stra ins exhibited similar distribution patterns for both binding sites, se ctions derived from SHR expressed a significant increase in the number of [H-3]pirenzepine binding sites compared to normotensive WKY in cau date putamen, CA3 region of the hippocampus, cingulate cortex, substan tia nigra, posterior hypothalamic area and tuberomammillary nucleus. A n increased number of [H-3]AFDX 384 binding sites in SHR were observed in the olfactory tubercle, nucleus accumbens, basolateral amygdaloid nucleus, rostroventrolateral medulla and nucleus paragigantocellularis . Decreases in the number of [H-3]AFDX 384 binding sites in SHR were a lso observed in the parietal cortex, medial geniculate, and lateral hy pothalamic area. Statistically significant site-selective differences in binding densities between strains ranged from 4.0% to 35.5% of WKY means. These alterations in the expression of M1 and M2 binding sites in cardiovascular regions may contribute to the strain's hyper-respons iveness to cholinergic drugs and possibly to the appearance of other a utonomic or behavioral phenotypes exhibited by SHR, including the hype rtensive state itself. (C) 1997 Elsevier Science B.V.