title: Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats.
abstract: Functional studies indicate that the sympathoexcitatory and pressor responses to an increase in cerebrospinal fluid (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 intracerebroventricular 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 intracerebroventricular infusion of aCSF or Na+-rich aCSF, in some groups combined with intracerebroventricular infusion of spironolactone (100 ng/h), antibody Fab fragments (to bind OLC), or as control gamma-globulins. After 2 wk of infusion, resting blood pressure and heart rate were recorded, OLC and aldosterone content in the hypothalamus were assessed by a specific ELISA or radioimmunoassay, and angiotensin-converting enzyme (ACE) and AT1-receptor binding densities in various brain nuclei were measured by autoradiography using 125I-labeled 351 A and 125I-labeled ANG II. When compared with intracerebroventricular aCSF, intracerebroventricular Na+-rich aCSF increased CSF [Na+] by approximately 5 mmol/l, mean arterial pressure by approximately 20 mmHg, heart rate by approximately 65 beats/min, and hypothalamic content of OLC by 50% and of aldosterone by 33%. Intracerebroventricular spironolactone did not affect CSF [Na+] but blocked the Na+-rich aCSF-induced increases in blood pressure and heart rate and OLC content. Intracerebroventricular 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 activate CNS pathways involving MR, and OLC, leading to increases in AT1-receptor and ACE densities in brain areas involved in cardiovascular regulation and hypertension.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, H360, 40 Ruskin St., Ottawa, Ontario, Canada K1Y 4W7.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Cheung
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Junhui
authors.initials: J
authors.lastname: Tan
authors.forename: Roselyn A
authors.initials: RA
authors.lastname: White
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000450:Aldosterone / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry; D002712:Chlorides / Q000134:cerebrospinal fluid; D053503:Epithelial Sodium Channels; D006339:Heart Rate / Q000502:physiology; D006400:Hematocrit; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011188:Potassium / Q000134:cerebrospinal fluid; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D012964:Sodium / Q000134:cerebrospinal fluid* / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
chemical_list: D002712:Chlorides; D053503:Epithelial Sodium Channels; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D000450:Aldosterone; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D011188:Potassium