Anterior hypothalamic β-adrenergic activity in the maintenance of hypertension in aortic coarctated rats

Abstract

The aim of this work was to demonstrate an alteration of the anterior hypothalamic catecholaminergic system in aortic coarctated (ACo) rats by the perfusion of β-adrenergic antagonist and the microinfusion of β-adrenergic agonist. Wistar urethane-chloralose anesthetized rats were used. The carotid artery was cannulated for blood pressure recording and changes in blood pressure were measured. A concentric microdialysis probe was inserted in the anterior hypothalamus. Metoprolol (a β1- adrenoceptor antagonist) perfusion (6μgml-1) reduced the mean arterial pressure (MAP) in the ACo rats but not in sham operated (SO) animals. The anterior hypothalamic infusion of non-specific β-adrenergic agonist isoproterenol induced a dose-dependent decrease of blood pressure in both experimental groups, but the depressor response was significantly lower in ACo rats. The pretreatment with atenolol, a selective β1- adrenoceptor antagonist, increased the depressor effect of isoproterenol in ACo rats, but not in SO rats. On the other hand, the hypotensive action of isoproterenol was significantly diminished after the administration of non-specific β-adrenoceptor antagonist propranolol in SO and ACo rats. The anterior hypothalamic infusion of clenbuterol, a selective β 2-adrenergic agonist, induced a dose-dependent decrease of blood pressure in both experimental groups. The depressor response to clenbuterol (1nmol) was significantly lower in ACo rats than in SO rats. In summary, this study provides the evidence that there is a β1-adrenergic compromise in anaesthetized ACo rats and this compromise may be involved in the maintenance of hypertension. On the other hand, this study also suggests the existence of pressor β1-adrenoceptors in the anterior hypothalamic area of ACo rats but not in SO rats. We also found a diminished depressor β2-adrenergic activity in ACo rats.