Abstract-There is substantial evidence that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity.We recently observed that nitric oxide and interleukin-1 (IL-1) 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-1 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-1. 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-1 and nNOS mRNA in the PH, PVN, and LC of normal Sprague-Dawley rats. Finally, we measured the concentration of nitrite/nitrate in the dialysate collected from the PH after Ang II or vehicle. ICV infusion of Ang II (100 ng/kg body wt dissolved in 10 L of artificial cerebrospinal fluid) raised BP, RSNA, and NE secretion from the PH compared with control rats. Ang II reduced the abundance of IL-1 and nNOS mRNA in the PH, PVN, and LC. Pretreatment with losartan (10 g/kg body wt dissolved in 10 L of aCSF) given ICV 20 minutes before Ang II abolished the effects of Ang II on BP, RSNA, and NE secretion from the PH and IL-1 and nNOS mRNA. Ang II also decreased the secretion of NO from the PH. In conclusion, these studies suggest that Ang II inhibits the expression of IL-1 and nNOS in the brain. Because locally produced NO exerts a tonic inhibitory action on SNS activity, the decrease in NO expression caused by Ang II results in greater SNS activity. Key Words: angiotensin II Ⅲ sympathetic nervous system Ⅲ losartan Ⅲ nitric oxide Ⅲ interleukins T here is substantial evidence that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity via actions on the brain, sympathetic ganglia, and sympathetic nerve endings. 1-9 The intracerebroventricular (ICV) administration of Ang II causes a dose-related increase in blood pressure (BP), 10 which is probably related to activation of Ang II type 1 (AT 1 ) receptors localized in the median preoptic nucleus and juxtaventricular neurons of the subfornical organ and organum vasculosum laminae terminalis 11,12 and the brain stem. 13 Ang II of central origin may activate peripheral sympathetic nerve activity trough a decrease of the arterial baroreceptor gain 14 or activation of preganglionic neurons in the rostral ventrolateral medulla (RVLM) or intermediolateral column. 15 Agents that inhibit the renin-angiotensin system (angiotensin-converting enzyme inhibitors and Ang II AT 1 -receptor antagonists) may provide important information on the effects and site of action of Ang I...
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