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Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats
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| Zeitschriftentitel: | American Journal of Physiology-Heart and Circulatory Physiology |
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| Personen und Körperschaften: | , , , , , |
| In: | American Journal of Physiology-Heart and Circulatory Physiology, 291, 2006, 3, S. H1109-H1117 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Physiological Society
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| Schlagwörter: |
| Zusammenfassung: | <jats:p> Functional studies indicate that the sympathoexcitatory and pressor responses to an increase in cerebrospinal fluid (CSF) [Na<jats:sup>+</jats:sup>] by central infusion of Na<jats:sup>+</jats:sup>-rich artificial cerebrospinal fluid (aCSF) in Wistar rats are mediated in the brain by mineralocorticoid receptor (MR) activation, ouabain-like compounds (OLC), and AT<jats:sub>1</jats:sub>-receptor stimulation. In the present study, we examined whether increasing CSF [Na<jats:sup>+</jats:sup>] by intracerebroventricular infusion of Na<jats:sup>+</jats:sup>-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<jats:sup>+</jats:sup>-rich aCSF, in some groups combined with intracerebroventricular infusion of spironolactone (100 ng/h), antibody Fab fragments (to bind OLC), or as control γ-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 AT<jats:sub>1</jats:sub>-receptor binding densities in various brain nuclei were measured by autoradiography using <jats:sup>125</jats:sup>I-labeled 351 A and <jats:sup>125</jats:sup>I-labeled ANG II. When compared with intracerebroventricular aCSF, intracerebroventricular Na<jats:sup>+</jats:sup>-rich aCSF increased CSF [Na<jats:sup>+</jats:sup>] by ∼5 mmol/l, mean arterial pressure by ∼20 mmHg, heart rate by ∼65 beats/min, and hypothalamic content of OLC by 50% and of aldosterone by 33%. Intracerebroventricular spironolactone did not affect CSF [Na<jats:sup>+</jats:sup>] but blocked the Na<jats:sup>+</jats:sup>-rich aCSF-induced increases in blood pressure and heart rate and OLC content. Intracerebroventricular Na<jats:sup>+</jats:sup>-rich aCSF increased ACE and AT<jats:sub>1</jats:sub>-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<jats:sup>+</jats:sup>] may increase hypothalamic aldosterone and activate CNS pathways involving MR, and OLC, leading to increases in AT<jats:sub>1</jats:sub>-receptor and ACE densities in brain areas involved in cardiovascular regulation and hypertension. </jats:p> |
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| Umfang: | H1109-H1117 |
| ISSN: |
0363-6135
1522-1539 |
| DOI: | 10.1152/ajpheart.00024.2006 |