Archives internationales de pharmacodynamie et de thérapie
-
Arch Int Pharmacodyn Ther · Oct 1987
Evidence for central alpha 2-adrenoceptor-mediated hypertension in freely moving, normotensive rats.
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 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)