title: Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone.
abstract: In rats with salt-induced hypertension or postmyocardial infarction, angiotensin II type 1 receptor (AT(1)R) densities and oxidative stress increase and neuronal NO synthase (nNOS) levels decrease in the paraventricular nucleus (PVN). The present study was designed to determine whether these changes may depend on activation of the aldosterone -'ouabain' neuromodulatory pathway. After intracerebroventricular (i.c.v.) infusion of aldosterone (20 ng h(-1)) for 14 days, blood pressure (BP) and heart rate (HR) were recorded in conscious Wistar rats, and mRNA and protein for nNOS, endothelial NO synthase (eNOS), AT(1)R and NADPH oxidase subunits were assessed in brain tissue. Blood pressure and HR were significantly increased by aldosterone. Aldosterone significantly increased mRNA and protein of AT(1)R, P22phox, P47phox, P67phox and Nox2, and decreased nNOS but not eNOS mRNA and protein in the PVN, as well as increased the angiotensin-converting enzyme and AT(1)R binding densities in the PVN and supraoptic nucleus. The increases in BP and HR, as well as the changes in mRNA, proteins and angiotensin-converting enzyme and AT(1)R binding densities were all largely prevented by concomitant i.c.v. infusion of Digibind (to bind 'ouabain') or benzamil (to block presumed epithelial sodium channels). These data indicate that aldosterone, via 'ouabain', increases in the PVN angiotensin-converting enzyme, AT(1)R and oxidative stress, but decreases nNOS, and suggest that endogenous aldosterone may cause the similar pattern of changes observed in salt-sensitive hypertension and heart failure postmyocardial infarction.
authors.affiliation: University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Junhui
authors.initials: J
authors.lastname: Tan
authors.forename: Kaushik P
authors.initials: KP
authors.lastname: Patel
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007140:Immunoglobulin Fab Fragments; D010750:Phosphoproteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; C050199:digoxin antibodies Fab fragments; C079789:neutrophil cytosol factor 67K; C013407:benzamil; D000450:Aldosterone; D000584:Amiloride; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1; D007703:Peptidyl-Dipeptidase A