Differential blood pressure responses to intracisternal clonidine, alpha-methyldopa, and 6-hydroxydopamine in conscious normotensive and spontaneously hypertensive rats

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 micrograms i.c.) and 6-OHDA (400 micrograms 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 rat that oppose their antihypertensive 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.