Downregulation of Neuronal Nitric Oxide Synthase and Interleukin-1β Mediates Angiotensin II-Dependent Stimulation of Sympathetic Nerve Activity

Abstract

— There is substantial evidence that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity. We recently observed that nitric oxide and interleukin-1β (IL-1β) exert a tonic inhibitory action on central SNS activity. Moreover, in 2 rat models of neurogenic hypertension, one caused by intrarenal injection of phenol and the other by 5/6 nephrectomy, we observed that losartan, an Ang II type 1 receptor blocker, inhibits SNS activity and increases the abundance of IL-1β and the neuronal isoform of nitric oxide synthase (nNOS) in the posterior hypothalamic nuclei (PH), paraventricular nuclei (PVN), and locus ceruleus (LC). This raises the possibility that the stimulatory effects of Ang II on central SNS activity may be mediated by inhibition of nNOS and IL-1β. To test this hypothesis, we studied the effect of an intracerebroventricular (ICV) infusion of Ang II on blood pressure (BP), norepinephrine (NE) secretion from the PH, renal SNS activity (RSNA), and abundance of IL-1β and nNOS...