Cardiovascular responses of sinoaortic-denervated rats to intracerebroventricular injection of α1- and α2-adrenoceptor agonists

Abstract

The aim of the present work was to analyse the cardiovascular responses induced by i.c.v. administration of the α 1- and α 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 μg) 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 α 2-adrenoceptors, but the blood pressure responses induced by clonidine in sinoaortic-denervated rats may also have involved α 1-adrenoceptors. The bradycardia induced by the α 2-agonist in both groups of rats involved preferentially central α 2-adrenoceptors but also partially stimulated α 1-adrenoceptors. Phenylephrine, at a dose of 10–60 μg, induced a rise in blood pressure and a bradycardiac response while 90 μg 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 α 1-adrenoceptors in every case, but the fall in blood pressure and the bradycardia also involved α 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 α-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.