Pressor response to microinjection of clonidine into the hypothalamic paraventricular nucleus in conscious rats

We have reported that intracerebroventricular (i.c.v.) injection of clonidine causes pressor response in conscious rats. To determine the effective brain site, cardiovascular responses induced by unilateral microinjection of clonidine into various hypothalamic nuclei of conscious rats were studied. Microinjection of clonidine (5-20 micrograms/0.5 microliter) into the paraventricular nucleus (PVN) of conscious rats dose-dependently produced a long-lasting pressor response with a decrease in heart rate, which mimicked the response to i.c.v. injection of clonidine. However, clonidine (10 micrograms) injection into various hypothalamic nuclei (anterior, posterior, ventromedial and dorsomedial nucleus) caused a small or no pressor response. In anesthetized rats, clonidine injected into the PVN induced a long-lasting depressor response concomitant with bradycardia. PVN pretreatment with the alpha 2-adrenoceptor antagonist, yohimbine (1 and 10 micrograms), dose-dependently inhibited the pressor response to PVN injected clonidine, but the alpha 1-adrenoceptor antagonist, prazosin (1 microgram), had no significant effect. Central (i.c.v.) pretreatment with the vasopressin (AVP) V1-receptor antagonist, [d(CH2)5Tyr(Me)]-AVP (0.5 and 2.0 micrograms), dose-dependently inhibited the pressor response to PVN injection of clonidine (10 micrograms), while systemic (i.v.) and local (intra-PVN injection) pretreatments with V1-receptor antagonist (2.0 micrograms) had no effect. These results suggest that the pressor response to microinjection of clonidine into the PVN of conscious rats is mediated by endogenous brain AVP, which is released by activation of alpha 2-adrenoceptors. It is also suggested that the PVN is a possible brain site for the pressor response to i.c.v. injected clonidine.