Evidence for central alpha 2-adrenoceptor-mediated hypertension in freely moving, normotensive rats

Abstract

The hypertensive response mediated by central alpha 2-adrenoceptor stimulation was investigated in freely moving, normotensive rats with chronic arterial catheters and guide cannulas. The alpha 1-adrenoceptor agonists (methoxamine, phenylephrine, ST 587) and the alpha 2-adrenoceptor agonists (B-HT 920, clonidine, oxymetazoline) injected intravenously (i.v.) caused a rise in mean blood pressure. The rank order of potency of the agonists to produce 25 mm Hg of pressor response (the effective dose; ED25) was oxymetazoline (0.64 microgram/kg) greater than phenylephrine (1.05 microgram/kg) greater than clonidine (1.6 microgram/kg) greater than ST 587 (5.4 micrograms/kg) greater than B-HT 920 (19.0 micrograms/kg) greater than methoxamine (19.5 micrograms/kg). The intracerebroventricular (i.c.v.) injection of alpha 2-adrenoceptor agonists, B-HT 920 (3 to 300 micrograms/kg), clonidine (3 to 100 micrograms/kg) and oxymetazoline (3 to 100 micrograms/kg) produced a dose-dependent and long-lasting pressor response associated with bradycardia, without showing a significant depressor response for up to 90 min at any of the doses used. The i.c.v. injection of alpha 1-adrenoceptor agonists, methoxamine (100 to 500 micrograms/kg), phenylephrine (100 to 500 micrograms/kg) and ST 587 (100 to 300 micrograms/kg) produced a short-lasting pressor response with variable changes in heart rate. In addition, a significant long-lasting depressor response concomitant with a decrease in heart rate was observed 30-60 min after the injection at higher doses. Dose-response curves for pressor responses to alpha 2-adrenoceptor agonists were located to the left of those for alpha 1-adrenoceptor agonists. The rank order of potency of the agonists injected i.c.v. in producing pressor responses with ED25 was clonidine (12.0 micrograms/kg) greater than oxymetazoline (14.0 micrograms/kg) greater than B-HT 920 (16.0 micrograms/kg) much greater than ST 587 (125 micrograms/kg) greater than phenylephrine (235 micrograms/kg) greater than methoxamine (310 micrograms/kg). Central (i.c.v.) pretreatment with yohimbine (100 micrograms/kg) abolished hypertensive responses to centrally administered alpha 2-adrenoceptor agonists but the treatment with prazosin (30 micrograms/kg) was less effective in inhibiting the hypertensive responses. In pentobarbital-anesthetized rats, pressor responses to i.c.v. injection of alpha 1- and alpha 2-adrenoceptor agonists were significantly inhibited and a long-lasting depressor response was induced by alpha 2-adrenoceptor agonists, whereas depressor responses to alpha 1-adrenoceptor agonists were not affected.(ABSTRACT TRUNCATED AT 400 WORDS)