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Renal sympathetic activation from long-term low-dose angiotensin II infusion in rabbits

Moretti, John-Luisa; Burke, Sandra L.a; Davern, Pamela J.a; Evans, Roger G.b; Lambert, Gavin W.a; Head, Geoffrey A.a,c

doi: 10.1097/HJH.0b013e328350133a
ORIGINAL PAPERS: Sympathetic mechanisms

Objective: Activation of renal sympathetic nerve activity (RSNA) has not been observed during long-term infusion of angiotensin II (AngII) which results in marked hypertension, despite activation of hypothalamic autonomic regions. We examined whether the function of central pathways influencing sympathetic activity is altered in conscious rabbits given a low dose of AngII that produces a modest hypertension and, therefore, limited secondary complications.

Methods: Rabbits received AngII (20–30 ng/kg per min, subcutaneously) or sham treatment for 3 months at which time they were implanted with a renal sympathetic nerve electrode and the responses to airjet stress, baroreflexes and hypoxia were examined.

Results: AngII infusion for 3 months increased mean arterial pressure by 16% and RSNA by 43%. Increases in RSNA during airjet stress and hypoxia (10% O2) were 35 and 65% greater in AngII-treated rabbits than sham controls, respectively. Tachycardic responses were also enhanced. Baroreflexes were shifted to the right and upward in the AngII animals but baroreflex gain was similar in the two groups, indicating near complete resetting. Greater neuronal Fos-related antigen immunoreactivity was found in the vascular organ of the lamina terminalis, paraventricular and supraoptic hypothalamic nuclei in AngII-treated rabbits compared with sham.

Conclusion: Our results suggest that low-dose AngII-treatment results in marked sympathetic activation at rest and during stress and hypoxia, due to activation of specific hypothalamic pathways. These mechanisms may contribute to sympathetic activation in conditions associated with chronic activation of the renin–angiotensin system such as obesity or renovascular disease.

aNeuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne

bDepartment of Physiology

cDepartment of Pharmacology, Monash University, Clayton, Victoria, Australia

Correspondence to Professor Geoffrey A. Head, Baker IDI Heart and Diabetes Institute, 75 Commercial Road Prahran, P.O. Box 6492, St Kilda Road Central, Melbourne, VIC 8008, Australia. Tel: +61 03 8532 1332; fax: +61 03 8532 1100; e-mail:

Abbreviations: AngII, angiotensin II; AT1, angiotensin II type 1 receptor; BP, blood pressure; FRA, Fos-related antigen; HR, heart rate; MAP, mean arterial pressure; MnPO, median preoptic nucleus; OVLT, vascular organ of the lamina terminalis; PRA, plasma renin activity; PVN, paraventricular nucleus; RBF, renal blood flow; RSNA, renal sympathetic nerve activity; SNS, sympathetic nervous system; SON, supraoptic nucleus

Received 18 August, 2011

Revised 3 November, 2011

Accepted 6 December, 2011

© 2012 Lippincott Williams & Wilkins, Inc.