Central alpha-2 adrenoceptor-mediated hypertensive response to clonidine in conscious, normotensive rats

Abstract

Possible involvement of central alpha-2 adrenoceptors in the hypertensive response to i.c.v. injected clonidine was investigated in free-moving, normotensive rats. Clonidine (2-50 micrograms) injected i.c.v. produced a dose-dependent and long-lasting pressor response associated with bradycardia in conscious rats, but a long-lasting depressor response in anesthetized rats. The pressor response to clonidine (20 micrograms i.c.v.) was antagonized in a dose-dependent manner by central (i.c.v.) pretreatment with yohimbine (20-100 micrograms) and was abolished by a high dose (100 micrograms), whereas the same dose of yohimbine injected i.v. had less effect on the response. Central pretreatment with prazosin (10 and 20 micrograms) inhibited, but did not abolish, the pressor response to clonidine. However, systemic (i.v.) pretreatment with the same dose of prazosin (10 and 20 mu) was more effective in reducing the clonidine-induced pressor response than central pretreatment with the drug. The pressor response to clonidine (20 micrograms i.c.v.) was not significantly modified by central pretreatment with pyrilamine (50 and 100 micrograms), cimetidine (50 and 100 micrograms), ketanserin (50 and 100 micrograms) or procaine (100 micrograms). The selective alpha-2 adrenoceptor agonist, BHT-920, injected i.c.v. (5-50 micrograms) also produced a dose-dependent pressor response which was abolished by either anesthesia or central pretreatment with yohimbine, but not with prazosin, whereas the selective alpha-1 adrenoceptor agonist, methoxamine (10-100 micrograms i.c.v.), caused a slight increase in mean blood pressure only at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)