Central alpha 1-adrenoceptors and cardiovascular control in normotensive and spontaneously hypertensive rats.

ABSTRACT

Intracerebroventricular (i.c.v.) injections of AR-C 239 (30 micrograms/kg), a selective alpha 1-adrenoceptor blocking drug, did not modify the heart rate in normotensive control (without pretreatment), bilaterally vagotomized and beta blocked rats and in spontaneously hypertensive (SH) bilaterally vagotomized rats. Intracisternal (i.c.) administrations of AR-C 239 (30 micrograms/kg) however decreased the heart rate in normotensive beta blocked and in SH bilaterally vagotomized rats. The differential effect on heart rate of i.c.v. versus i.c. administration of AR-C 239 suggests a brainstem localization of the alpha 1-adrenoceptors involved. The binding of [3H]prazosin was significantly higher in homogenates from whole brain and in membranes from the cerebral cortex and hypothalamus of SH rats as compared to normotensive rats. In addition, the binding of [125I]BE 2254, a new iodinated radioligand of high specific radioactivity used to characterize alpha 1-adrenoceptors, was significantly increased in membranes from the NTS of SH rats. These results suggest that central alpha 1-adrenoceptors localized in the brainstem and in the hypothalamus and the cortex play a role in the control of vagal tone in normotensive rats and of sympathetic activity in SH animals. Thus, it is postulated that central alpha 1-adrenoceptors may participate in either the genesis or the maintenance of genetic hypertension.