Abstract 420: Role of Ang II and Glutamate in the PVN of Rats with Ang II-induced Hypertension

Abstract

A chronic increase in circulating Ang II increases neuronal activation in hypothalamic nuclei such as the paraventricular nucleus (PVN) and causes progressive hypertension. These effects can be largely prevented by central infusion of blockers of an aldosterone-ouabain neuromodulatory pathway that enhances the activity of angiotensinergic sympathoexcitatory pathways. A number of models of chronic sympathetic hyperactivity are associated with an increase in glutamate receptor and AT 1 -receptor activation in the PVN. The present study evaluated whether these mechanisms in the PVN also contribute to the elevated BP from a chronic increase in plasma Ang II by chronic subcutaneous (sc) infusion of Ang II for 2 weeks. One week following bilateral stereotaxic cannulation of the PVN, bilateral infusion (300 nL/min/side) of AT 1 and glutamate receptor blockers, candesartan and kynurenate were performed, and BP and HR were recorded in conscious Wistar rats. Data are mean±SE; (n=4-5/group). *p<0.05 vs. baseline Kynurenate or candesartan in the PVN both fully reversed the increase in BP from sc infusion of Ang II for 2 weeks. Infusion of candesartan after kynurenate or kynurenate after candesartan did not further lower BP. These findings suggest that enhanced AT 1 -receptor and glutamate receptor activation in the PVN both contribute to the elevated BP in Wistar rats with chronically elevated plasma Ang II. The effects of increased AT 1 -receptor activation in the PVN appear to be mediated by local glutamate release.