Cardiovascular responses of sinoaortic-denervated rats to intracerebroventricular injection of alpha 1- and alpha 2-adrenoceptor agonists.
The aim of the present work was to analyse the cardiovascular responses induced by i.c.v. administration of the alpha 1- and alpha 2-adrenoceptor agonists, phenylephrine and clonidine, respectively, in conscious normal and sinoaortic-denervated rats. Sinoaortic denervation involves changes in central and peripheral catecholaminergic pathways. Clonidine (1-10 micrograms) produced a dose-dependent rise in blood pressure and a bradycardiac response in sham-operated animals, whereas in sinoaortic-denervated rats it provoked a brief rise in blood pressure followed by a marked fall as well as bradycardia. The responses involved mostly activation of central alpha 2-adrenoceptors, but the blood pressure responses induced by clonidine in sinoaortic-denervated rats may also have involved alpha 1-adrenoceptors. The bradycardia induced by the alpha 2-agonist in both groups of rats involved preferentially central alpha 2-adrenoceptors but also partially stimulated alpha 1-adrenoceptors. Phenylephrine, at a dose of 10-60 micrograms, induced a rise in blood pressure and a bradycardiac response while 90 micrograms produced a biphasic pressure response (early transient rise followed by a fall) as well as bradycardia in both sham-operated and sinoaortic-denervated animals. Phenylephrine activated alpha 1-adrenoceptors in every case, but the fall in blood pressure and the bradycardia also involved alpha 2-adrenoceptors. The responses were significantly higher in the sinoaortic-denervated rats than in the sham-operated. Our findings suggest that arterial baroreceptor reflexes can modify the effects of alpha-agonists initiated in the central nervous system. Sinoaortic denervation preparations enable one to unmask the depressor response to clonidine and also demonstrate the true magnitude of the phenylephrine response.
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Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, UBA, CONICET, Buenos Aires, Argentina.
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D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003714:Denervation; D004146:Dioxanes / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D019329:Idazoxan; D007276:Injections, Intraventricular; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010656:Phenylephrine; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan