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Am J Physiol Regul Integr Comp Physiol 286: R1051-R1056, 2004. First published January 29, 2004; doi:10.1152/ajpregu.00708.2003
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NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION

Stimulation of cardiac sympathetic nerve activity by central angiotensinergic mechanisms in conscious sheep

Anna M. D. Watson,1 Rasim Mogulkoc,2 Robin M. McAllen,1 and Clive N. May1

1Howard Florey Institute of Physiology and Medicine, University of Melbourne, Parkville 3010, Australia; and 2Selcuk University Medical School, Department of Physiology, 42090 Konya, Turkey

Submitted 11 December 2003 ; accepted in final form 27 January 2004

Central actions of angiotensin play an important role in cardiovascular control and have been implicated in the pathogenesis of hypertension and heart failure. One feature of centrally or peripherally administered angiotensin is that the bradycardia in response to an acute pressor effect is blunted. It is unknown whether after central angiotensin this is due partly to increased cardiac sympathetic nerve activity (CSNA). We recorded CSNA and arterial pressure in conscious sheep, at least 3 days after electrode implantation. The effects of intracerebroventricular infusions of ANG II (3 nmol/h for 30 min) and artificial cerebrospinal fluid (CSF) (1 ml/h) were determined. The response to intracerebroventricular hypertonic saline (0.6 M NaCl in CSF at 1 ml/h) was examined as there is evidence that hypertonic saline acts via angiotensinergic pathways. Intracerebroventricular angiotensin increased CSNA by 23 ± 7% (P < 0.001) and mean arterial pressure (MAP) by 7.6 ± 1.2 mmHg (P < 0.001) but did not significantly change heart rate (n = 5). During intracerebroventricular ANG II the reflex relation between CSNA and diastolic blood pressure was significantly shifted to the right (P < 0.01). Intracerebroventricular hypertonic saline increased CSNA (+9.4 ± 6.6%, P < 0.05) and MAP but did not alter heart rate. The responses to angiotensin and hypertonic saline were prevented by intracerebroventricular losartan (1 mg/h). In conclusion, in conscious sheep angiotensin acts within the brain to increase CSNA, despite increased MAP. The increase in CSNA may account partly for the lack of bradycardia in response to the increased arterial pressure. The responses to angiotensin and hypertonic saline were losartan sensitive, indicating they were mediated by angiotensin AT-1 receptors.

angiotensin II; baroreflex; hypertonic saline; intracerebroventricular; losartan



Address for reprint requests and other correspondence: C. N. May, Howard Florey Institute, Univ. of Melbourne, Parkville 3010, Victoria, Australia (E-mail: c.may{at}hfi.unimelb.edu.au).




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