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Am J Physiol Heart Circ Physiol (April 7, 2006). doi:10.1152/ajpheart.00024.2006
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Submitted on January 5, 2006
Accepted on March 28, 2006

Activation of the brain renin-angiotensin-aldosterone system by central sodium in Wistar rats

Bing S Huang1, Warren J Cheung1, Hao Wang2, Junhui Tan1, Roselyn A White1, and Frans H. Leenen1*

1 Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Canada
2 Medicine, Duke University Medical Center, Durham, North Carolina, United States

* To whom correspondence should be addressed. E-mail: fleenen{at}ottawaheart.ca.

Functional studies indicate that the sympatho-excitatory and pressor responses to an increase in CSF [Na+] by central infusion of Na+-rich artificial cerebrospinal fluid (aCSF) in Wistar rats are mediated in the brain by mineralocorticoid receptor (MR) activation, ouabain-like compounds (OLC) and AT1-receptor stimulation. In the present study, we examined whether increasing CSF [Na+] by icv infusion of Na+-rich aCSF activates MR and thereby increases OLC and components of the renin-angiotensin system in the brain. Male Wistar rats received via osmotic minipump an icv infusion of aCSF or Na+-rich aCSF, in some groups combined with icv infusion of spironolactone (100 ng/hr), antibody Fab fragments (to bind OLC) or as control {gamma}-globulins. After 2 wks of infusion, resting BP and HR were recorded, OLC and aldosterone content in the hypothalamus were assessed by a specific ELISA or radio-immunoassay, and angiotensin-converting enzyme (ACE) and AT1-receptor binding densities in various brain nuclei measured by autoradiography using 125I-labelled 351 A and 125I-labelled Ang II. Compared to icv aCSF, icv Na+-rich aCSF increased CSF [Na+] by ~5 mmol/L, MAP by ~20 mmHg, HR by ~65 bpm, and hypothalamic content of OLC by 50% and of aldosterone by 33%. Icv spironolactone did not affect CSF [Na+], but blocked the Na+- rich aCSF induced increases in BP and HR and OLC content. Icv Na+-rich aCSF increased ACE and AT1-receptor binding densities in several brain nuclei, and Fab fragments blocked these increases. These data indicate that in Wistar rats, a chronic increase in CSF [Na+] may increase hypothalamic aldosterone and activates CNS pathways involving MR, and OLC, leading to increases in AT1-receptor and ACE densities in brain areas involved in cardiovascular regulation and hypertension.




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