Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats.
In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na(+) concentration ([Na(+)]) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na(+)] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by approximately 35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by approximately 65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na(+)]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension.
Huang
Bing S
BS
University of Ottawa Heart Institute, Ottawa, ON, Canada K1Y 4W7.
White
Roselyn A
RA
Jeng
Arco Y
AY
Leenen
Frans H H
FH
D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D019405:Cytochrome P-450 CYP11B2; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006339:Heart Rate; D006624:Hippocampus / Q000201:enzymology; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D051381:Rats; D020303:Rats, Inbred Dahl; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012964:Sodium / Q000134:cerebrospinal fluid*; D017673:Sodium Chloride, Dietary / Q000378:metabolism; D013148:Spironolactone / Q000008:administration & dosage; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D000450:Aldosterone; D012964:Sodium; D013250:Steroid Hydroxylases; C120361:Cyp11b3 protein, rat; D019405:Cytochrome P-450 CYP11B2; D003345:Corticosterone