Hypothalamic angiotensinergic-noradrenergic systems interaction in fructose induced hypertension

MAYER MA, HÖCHT C, GIRONACCI MM, OPEZZO JAW, TAIRA CA, FERNÁNDEZ BE, PUYÓ AM

REGULATORY PEPTIDES

Elsevier

Año: 2008 vol. 146 p. 38 - 45

0167-0115

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 (AT1 angiotensin receptor antagonist, 50 and 500 μg ml− 1) and metoprolol (β1 adrenergic receptor antagonist, 10 and 100 μg 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 (ΔMAP: F: − 16.3±1 mm Hg, pb0.05) and noradrenaline levels (% of basal levels: 58±7%, pb0.05) in the F group, without affecting heart rate. Intrahypothalamic perfusion of metoprolol diminished MAP only in the F group (ΔMAP: F: − 12.1±1.1 mm Hg, pb0.05), 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%, pb0.05) but not in the F group. The pressor response to angiotensin II microinjection was increased in F rats (ΔMAP: F: 13.3±1.5 mm Hg vs. C: 6.9±1.8 mm Hg; pb0.05). Previous administration of metoprolol markedly abolished this increment. Conclusions: Our results suggest the existence of an increase in AT1 and β1 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 β1 adrenergic receptor antagonist, these results would indicate that β1 adrenergic receptors activation participates in the pressor response to angiotensin II in this experimental model of insulin resistance and hypertension .