Central and peripheral renin-angiotensin systems in ouabain-induced hypertension.
Chronic subcutaneous infusion of ouabain causes hypertension via central pathways involving angiotensin type 1 (AT(1)) receptor stimulation. The present study assessed plasma and tissue ANG I and II levels as well as AT1 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 wk after start of ouabain infusion at 50 microg/day. After 2 wk (but not after 1 wk), blood pressures significantly increased (+15 mmHg). At 2 wk, plasma ANG I and II levels were markedly suppressed by ouabain. 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. At 1 wk, no changes in ACE and AT1 receptor densities were seen. After 2 wk, there were significant decreases in AT(1) receptor mRNA and densities in the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and paraventricular nucleus (PVN). ACE densities decreased only in the OVLT and SFO, but ACE mRNA showed more variable responses (decrease in OVLT vs. increase in PVN). In the kidneys, at 2 wk both AT1 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 AT1 receptor and ACE densities support the involvement of the brain renin-angiotensin system in the central hypertensive mechanism of action of ouabain.
Hypertension Unit, Univ. of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7.
Warren J
WJ
Cheung
Mary-Anne H
MA
Kent
Esraa
E
El-Shahat
Hongwei
H
Wang
Junhui
J
Tan
Roselyn
R
White
Frans H H
FH
Leenen
D000803:Angiotensin I / Q000502:physiology; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D002316:Cardiotonic Agents / Q000097:blood; D002490:Central Nervous System / Q000502:physiology*; D006321:Heart / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology; D008297:Male; D010042:Ouabain / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis; D017933:Peripheral Nervous System / Q000502:physiology*; D011301:Preoptic Area / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013356:Subfornical Organ / Q000502:physiology
D002316:Cardiotonic Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D010042:Ouabain; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin