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Central and peripheral renin‐angiotensin systems in ouabain‐induced hypertension 1
Author(s) -
Leenen Frans H.H.,
Cheung Warren J.,
Kent MaryAnne H.,
ELShahat Esraa,
Wang Hongwei,
Tan Junhui,
White Roselyn
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1205-b
Subject(s) - subfornical organ , medicine , endocrinology , angiotensin ii receptor type 1 , ouabain , renin–angiotensin system , angiotensin ii , chemistry , receptor , hypothalamus , stimulation , kidney , blood pressure , sodium , organic chemistry
Chronic subcutaneous infusion of ouabain causes hypertension via central pathways involving AT 1 receptor stimulation. The present study assessed plasma and tissue Ang I and II levels as well as AT 1 receptor and angiotensin converting enzyme (ACE) mRNA levels and binding densities by real–time PCR and in vitro autoradiography in relevant brain nuclei and peripheral tissues (heart and kidney) in rats at 1 and/or 2 weeks after start of ouabain infusion at 50 μg/day. After 2 weeks (but not after 1 week) blood pressures significantly increased (+15 mmHg). At 2 weeks, plasma Ang II levels were markedly suppressed by ouabain from 15 ± 4 to 3 ± 1 pg/ml. In contrast, in the heart and kidneys Ang I levels were not affected and Ang II levels tended to decrease, whereas in the hypothalamus Ang II content clearly increased from 3 ± 2 to 18 ± 6 pg/g. At 1 week, no changes in ACE and AT 1 receptor densities were seen. After 2 weeks, there were significant decreases in AT 1 receptor mRNA by 30–50% and densities by ~15% in the organum vasculosum of the laminae terminalis (OVLT), subfornical organ (SFO) and paraventricular nucleus (PVN), as well as decreases in ACE densities in the OVLT and SFO by 25–50%. In the kidneys, at 2 weeks both AT 1 receptor and ACE densities were decreased but mRNA abundance did not change. The heart showed no significant changes. The increase in hypothalamic Ang II content and associated decreases in central AT 1 receptor and ACE densities support the involvement of the brain RAS in the central hypertensive mechanism of action of ouabain.