DIFFERENTIAL BLOOD-PRESSURE RESPONSES TO INTRACISTERNAL CLONIDINE, ALPHA-METHYLDOPA, AND 6-HYDROXYDOPAMINE IN CONSCIOUS NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

  • 1 January 1986
    • journal article
    • research article
    • Vol. 8  (4) , 735-742
Abstract
The cardiovascular effects of three drugs that activate central .alpha.-adrenoceptor mechanisms were investigated in conscious normotensive Wistar and Wistar-Kyoto rats, and in spontaneously hypertensive rats (SHR). From dose-response curves, near-maximal intracisternal (i.c.) depressor doses of clonidine, .alpha.-methyldopa (.alpha.-MD), and 6-hydroxydopamine (6-OHDA; a neurotoxic agent that acutely releases central noradrenaline) were determined. In all three strains of rats, .alpha.-MD (1 mg i.c.) produced a 23-25% reduction in blood pressure. Clonidine (2.5 .mu.g i.c.) and 6-OHDA (400 .mu.g i.c.) produced similar falls in blood pressure in SHR to that observed with .alpha.-MD, but they were much less effective in normotensive rats (7 and 13%, respectively, in Wistar; 22 and 21% in SHR). Higher doses of clonidine increased blood pressure in Wistar rats, but further reduced it in SHR. The late pressor response observed 2-3 h after 6-OHDA administration in Wistar rats was not observed in SHR. These results support the view that clonidine and 6-OHDA, but not .alpha.-MD, have central pressor actions in the rats that oppose their antihypertnesive action. The absence of this pressor effect in SHR indicates that there are significant differences in central noradrenergic pathways and .alpha.-adrenoceptor distribution among the three strains of rats.