Role of hypothalamic alpha-adrenoceptor activity in fructose-induced hypertension.
The aim of the present study was to investigate the effects of the alpha2-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 microg/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 (DeltaMAP 9 +/- 1 and 11 +/- 2 mmHg for 10 and 100 microg/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 microg/mL yohimbine increased DOPAC levels in C rats (135 +/- 6 and 130 +/- 5% of basal levels, respectively; both n = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 +/- 6 and 102 +/- 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 alpha2-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 alpha2-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 alpha2-adrenoceptor activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not differ between C and F groups.
Mayer
Marcos A
MA
Department of Macro and Microscopic Anatomy, University of Buenos Aires, Buenos Aires, Argentina. marcos.mayer@gmail.com
Höcht
Christian
C
Opezzo
Javier Aw
JA
Peredo
Horacio A
HA
Navacchia
Daniel
D
Taira
Carlos A
CA
Fernández
Belisario E
BE
Puyó
Ana M
AM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects; D000917:Antibody Formation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005632:Fructose; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced*; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010477:Perfusion / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism* / Q000502:physiology*; D011985:Receptors, Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D015102:3,4-Dihydroxyphenylacetic Acid; D015016:Yohimbine; D005632:Fructose; D006897:Hydroxyindoleacetic Acid