Differences in the ability of yohimbine to antagonize the hypotensive effect of clonidine in normotensive and spontaneously hypertensive anesthetized rats.

Low doses of yohimbine (1, 5 and 10 micrograms/kg), injected i.c.v. to spontaneously hypertensive rats as pretreatment, prevented the hypotensive effect of clonidine (standard dose of 5 micrograms/kg). At the opposite, the same doses of yohimbine did not influence the hypotensive effect of clonidine in control groups of normotensive animals (Wistar-Kyoto rats) treated under the same conditions. Interestingly, we observed that the central hypotensive effect of clonidine was greater in the hypertensive animals than in normotensive rats. Thus, we concluded that the central hypotensive effect of clonidine is affected by very low doses of yohimbine in spontaneously hypertensive rats and not in normotensive control animals. The yohimbine insensitive effect might be due to the action of clonidine on one type of medullary receptors specific to the imidazoline structure. On the physiopathological side, it seems therefore that, in hypertensive animals, there is a yohimbine sensitive mechanism, perhaps an alpha-2 adrenoceptor stimulating effect, which is nonexistent in normotensive animals.