Effects of the alpha 2-adrenoceptor agonist UK14304 on pressor responses in pithed rats.
1. Intravenous infusions of UK14304 (0.3-10 micrograms/kg per min) in pithed rat produced dose-dependent pressor responses which were not affected by prazosin (10 micrograms/kg) but were reduced by yohimbine (0.3 mg/kg). 2. Pressor responses to noradrenaline (0.1 micrograms/kg), phenylephrine (1 micrograms/kg) and vasopressin (10 mU/kg) were enhanced during infusions of UK14304 (0.03-1 micrograms/kg per min). Likewise, pressor responses to spinal sympathetic stimulation were enhanced during infusions of low concentrations of UK14304 (0.03-0.3 microgram/kg per min) but were reduced during infusion of a higher concentration of UK14304 (10 micrograms/kg per min). 3. After administration of yohimbine (0.3 mg/kg) or the calcium channel blocking drug diltiazem (infused at 50 micrograms/kg per min), pressor responses to noradrenaline and UK14304 were reduced, and responses to noradrenaline during infusion of UK14304 were not enhanced. 4. Prazosin (10 micrograms/kg) revealed a secondary depressor component in the response to sympathetic stimulation which is due to beta-adrenoceptor activation, since it was abolished by ICI 118551 (0.3 mg/kg). In the presence of ICI 118551 plus prazosin, pressor responses to sympathetic stimulation were enhanced during infusions of UK14304. 5. The depressor response to nitroprusside and the depressor component of responses to sympathetic stimulation after prazosin were enhanced during infusions of UK14304 at concentrations that increased the blood pressure. 6. The findings show that alpha 2-adrenoceptor activation enhanced the pressor responses to sympathetic nerve stimulation, noradrenaline, phenylephrine and vasopressin in the pithed rat and beta-adrenoceptor activation produced depressor responses which increased with increasing blood pressure.
Xiao
X H
XH
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Rand
M J
MJ
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D003655:Decerebrate State / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D014667:Vasopressins / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D014667:Vasopressins; D010656:Phenylephrine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D009638:Norepinephrine; D011224:Prazosin