Cholinergic hyperactivity in the lateral septal area of spontaneously hypertensive rats: Depressor effect of hemicholinium-3 and pirenzepine

In the lateral septal area of spontaneously hypertensive rats, but not in Wistar-Kyoto rats, the selective M 1 antagonist, pirenzepine, and the depletion of acetylcholine storage, by hemicholinium-3 (HC-3), decreased blood pressure. The selective M 1 agonist McNeil-A-343, produced a pressor response only after treatment of the lateral septal area with HC-3 in spontaneously hypertensive rats. Carbachol, at doses that mainly affect M 2 muscarinic receptors, caused no cardiovascular changes in either strain, pointing to the main intervention of the M 1 subtype of muscarinic receptor in the hypertensive condition. In addition, increases in the density of binding sites for [ 3H]QNB and in V max of sodium-dependent, HC-3-inhibitable, high affinity uptake of choline were demonstrated, without significant changes of the activity of choline acetyltransferase in the lateral septal area of spontaneously hypertensive rats. These results suggest that a hyperactivity of the cholinergic system of this area could play a role in the development and/or maintenance of hypertension in spontaneously hypertensive rats.