Role of Hypothalamic alpha sub(2)-Adrenoceptor Activity in Fructose-Induced Hypertension

The aim of the present study was to investigate the effects of the alpha sub(2)-adrenoceptor antagonist yohimbine on blood pressure and heart rate (HR) regulation, as well as on adrenergic and serotoninergic neurotransmission, in fructose hypertensive (F) rats. The anterior hypothalamic area of control (C) and F rats was perfused with Ringer's solution containing 10 and 100 mu g/mL yohimbine through a microdialysis concentric probe. The effects of yohimbine on mean arterial pressure (MAP) and HR, as well as on hypothalamic dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) levels, were measured according to perfusion time. Although intrahypothalamic perfusion of yohimbine increased blood pressure in C rats ( Delta MAP 9 plus or minus 1 and 11 plus or minus 2 mmHg for 10 and 100 mu g/mL yohimbine, respectively; P < 0.05 vs Ringer's perfusion), the alpha -adrenoceptor antagonist did not modify MAP in F. Intrahypothalamic yohimbine had no effect on HR at either concentration tested. Intrahypothalamic perfusion of 10 and 100 mu g/mL yohimbine increased DOPAC levels in C rats (135 plus or minus 6 and 130 plus or minus 5% of basal levels, respectively; both n = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 plus or minus 6 and 102 plus or minus 6% of basal levels, respectively; both n = 6). In both C and F rats, yohimbine administration induced an increase in 5-HIAA dialysate levels. The results of the present study support the notion that alpha sub(2)-adrenoceptor tone of the anterior hypothalamus of normotensive rats, which contributes to normal blood pressure regulation, is not involved in the control of HR in either normotensive C or hypertensive F rats. The absence of changes in MAP after yohimbine perfusion in F rats suggests that the alpha sub(2)-adrenoceptor tone could be decreased in this group of rats and that this may be responsible for the maintenance of hypertension in this model. Intrahypothalamic perfusion of yohimbine increased DOPAC in the dialysate only in C rats, suggesting changes in presynaptic alpha sub(2)-adrenoceptor activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not differ between C and F groups.