Brain nicotine cholinoceptor binding in spontaneous hypertension

To study the role of central cholinergic mechanisms in hypertension, we have determined nicotinic and muscarinic agonist binding sites in the brain regions of stroke-prone spontaneously hypertensive rats (SHRSP), using [3H]nicotine and [3H]cismethyldioxolane (CD). There was a significant decrease in specific [3H]nicotine binding in the cerebral cortex, thalamus, midbrain, cerebellum and medulla oblongata of SHRSP at 16-24 weeks of age compared to that of age-matched Wistar Kyoto rats (WKY). Scatchard analysis revealed 35% decrease in the Bmax value for [3H]nicotine binding in the SHRSP medulla oblongata without a change in the Kd value, suggesting a change in the receptor density. Similar reduction of nicotinic cholinoceptor binding sites was also observed in the discrete brain regions of young (5-week-old) SHRSP. In contrast, there was no alteration in specific [3H]CD binding in the SHRSP brains regions, except the hypothalamus which showed a significant increase. The SHRSP medulla oblongata showed no change in the ChAT activity. Thus, the present study suggests an important role for medullary nicotinic cholinoceptors in the pathogenesis of spontaneous hypertension.