Hypothalamic angiotensinergic-noradrenergic systems interaction in fructose induced hypertension.
OBJECTIVE
Several studies suggest the importance of the interaction between the renin angiotensin and sympathetic nervous systems in blood pressure control, especially in clinical situations such as the metabolic syndrome. Previously, we have demonstrated changes in noradrenergic hypothalamic control of blood pressure in an animal model of insulin resistance and hypertension. The aim of the present study was to evaluate the effects of the interaction between the noradrenergic and angiotensinergic systems on hypothalamic blood pressure regulation in fructose hypertensive rats.


METHODS
In control (C) and fructose-fed hypertensive (F) rats, we studied: 1) the effects of hypothalamic perfusion of irbesartan (AT(1) angiotensin receptor antagonist, 50 and 500 microg ml(-1)) and metoprolol (beta(1) adrenergic receptor antagonist, 10 and 100 microg ml(-1)) on blood pressure, heart rate and noradrenaline intrahypothalamic levels, by means of the microdialysis technique; and 2) the effects of intrahypothalamic microinjection of angiotensin II alone or after metoprolol pre-administration, on blood pressure and heart rate.


RESULTS
Meanwhile irbesartan perfusion did not modify neither mean arterial pressure (MAP) nor heart rate or noradrenaline hypothalamic levels in the C group, its highest dose diminished MAP (DeltaMAP: F: - 16.3+/-1 mm Hg, p<0.05) and noradrenaline levels (% of basal levels: 58+/-7%, p<0.05) in the F group, without affecting heart rate. Intrahypothalamic perfusion of metoprolol diminished MAP only in the F group (DeltaMAP: F: -12.1+/-1.1 mm Hg, p<0.05), but did not modify heart rate in both groups. On the other hand, it diminished noradrenaline hypothalamic levels in C (% of basal levels: 53+/-6%, p<0.05) but not in the F group. The pressor response to angiotensin II microinjection was increased in F rats (DeltaMAP: F: 13.3+/-1.5 mm Hg vs. C: 6.9+/-1.8 mm Hg; p<0.05). Previous administration of metoprolol markedly abolished this increment.


CONCLUSIONS
Our results suggest the existence of an increase in AT(1) and beta(1) adrenergic receptors tone in the hypothalamus of F rats, which could be related to the increase in blood pressure present in this experimental model. On the other hand, considering that the enhanced pressor response to angiotensin II intrahypothalamic injection in F rats was abolished by previous administration of a beta(1) adrenergic receptor antagonist, these results would indicate that beta(1) adrenergic receptors activation participates in the pressor response to angiotensin II in this experimental model of insulin resistance and hypertension.
Mayer
Marcos A
MA
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956, (C1113AAD), Buenos Aires, Argentina. marcos.mayer@gmail.com
Höcht
Christian
C
Gironacci
Mariela
M
Opezzo
Javier A W
JA
Taira
Carlos A
CA
Fernández
Belisario E
BE
Puyó
Ana M
AM
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007333:Insulin Resistance; D000077405:Irbesartan; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011945:Receptors, Angiotensin / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology