title: Role of brain corticosterone and aldosterone in central angiotensin II-induced hypertension.
abstract: Circulating angiotensin II (Ang II) activates a central aldosterone-mineralocorticoid receptor neuromodulatory pathway, which mediates most of the Ang II-induced hypertension. This study examined whether specific central infusion of Ang II also activates this central aldosterone-mineralocorticoid receptor pathway. Intracerebroventricular infusion of Ang II at 1.0, 2.5, and 12.5 ng/min for 2 weeks caused dose-related increases in water intake, Ang II concentration in the cerebrospinal fluid, and blood pressure. Intracerebroventricular Ang II, at 2.5 and 12.5 ng/min, increased hypothalamic aldosterone and corticosterone, as well as plasma aldosterone and corticosterone without affecting plasma Ang II levels. Intracerebroventricular infusion of the aldosterone synthase inhibitor FAD286-but not the mineralocorticoid receptor blocker eplerenone-inhibited by ≈60% the Ang II-induced increase in hypothalamic aldosterone. Both blockers attenuated by ≈50% the increase in plasma aldosterone and corticosterone with only minimal effects on hypothalamic corticosterone. By telemetry, intracerebroventricular infusion of Ang II maximally increased blood pressure within the first day with no further increase over the next 2 weeks. Intracerebroventricular infusion of FAD286 or eplerenone did not affect the initial pressor responses but similarly prevented 60% to 70% of the chronic pressor responses to intracerebroventricular infusion of Ang II. These results indicate distinctly different patterns of blood pressure increase by circulating versus central Ang II and support the involvement of a brain aldosterone-mineralocorticoid receptor-activated neuromodulatory pathway in the chronic hypertension caused by both circulating and central Ang II.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, H3238-40 Ruskin St, Ottawa, Ontario K1Y 4W7, Canada.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Roselyn A
authors.initials: RA
authors.lastname: White
authors.forename: Monir
authors.initials: M
authors.lastname: Ahmad
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D000077545:Eplerenone; D017316:Fadrozole / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D019405:Cytochrome P-450 CYP11B2; D017316:Fadrozole; D003345:Corticosterone
keywords: aldosterone synthase; cerebrospinal fluid; eplerenone; infusions, central or intracerebroventricular