Effect of hypertension and age on alpha 1-adrenoceptors in rat brain: modulation of [3H] prazosin binding by chronic treatment with desipramine and AR-C239.

The influence of repeated treatment with desipramine or AR-C239 on cerebral cortex alpha 1-adrenoceptors of mature (4 months), senescent (24 months) Wistar-Kyoto and mature spontaneously hypertensive rats was measured using [3H] prazosin as a ligand. Chronic desipramine treatment had no effect on [3H] prazosin binding in mature and aged Wistar-Kyoto rats but significantly decreased it in spontaneously hypertensive rats. Repeated AR-C239 treatment did not alter [3H] prazosin binding in senescent Wistar-Kyoto and mature spontaneously hypertensive rats, but significantly increased the [3H] prazosin binding density in mature Wistar-Kyoto rats. Thus, cortical alpha 1-adrenoceptors are not up-regulated by a decreased noradrenergic activity in aged or hypertensive rats as is the case in mature normotensive rats. In addition, these receptors are down-regulated by an increased noradrenergic activity in hypertensive rats only. These results suggest that the synthesis of alpha 1-adrenoceptors is impaired with age or with genetic hypertension and their degeneration is exacerbated with genetic hypertension in response to a changing environment.