Effect of intravenous angiotensin II infusion on responses to hypothalamic PVN injection of bicuculline.

Abstract

The hypothalamic paraventricular nucleus (PVN) plays an important role in the sympathoexcitatory response to elevated plasma angiotensin II (Ang II). However, the mechanism by which Ang II influences sympathetic activity is not fully understood. In this study, we tested the hypothesis that GABA(gamma-aminobutyric acid)-ergic function in the PVN is reduced by peripheral infusion of Ang II. To accomplish this, rats received either intravenous Ang II (12 ng/kg per minute) or vehicle (D5W) for 7 days, and renal sympathetic nerve activity (SNA), mean arterial pressure (MAP), and heart rate (HR) responses were recorded after unilateral PVN microinjection of the GABA-A receptor antagonist bicuculline methiodide (BMI, 0.1 nmol). Results indicate that in contrast to a significant increase in renal SNA, MAP, and HR observed in vehicle-infused rats (P<0.05), BMI injection into the PVN of Ang II-infused animals was without effect on all recorded variables. In a separate groups of animals, ganglionic blockade produced a significantly greater fall in MAP (P<0.01) in Ang II-infused rats than in vehicle-infused control rats, indicating that the contribution of SNA to the maintenance of blood pressure was elevated in the Ang II-infused group. Overall, these data indicate that cardiovascular and sympathoexcitatory responses to acute GABA-A receptor antagonism in the PVN are significantly blunted in rats after 7 days of intravenous infusion of Ang II. We conclude that an Ang II-induced reduction in GABAergic inhibition within the PVN may contribute to elevated SNA observed in this study.