Ouabain-induced hypertension in the rat: Relationships among plasma and tissue ouabain and blood pressure

Paolo Manunta, Amy C. Rogowski, Bruce P. Hamilton, John M. Hamlyn

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Objectives: To determine the steady-state dose-dependence of blood pressure, plasma and tissue ouabain during continuous infusion of ouabain in the rat, and to evaluate the adrenal dependence and effect of a high salt intake on this form of hypertension. Design and methods: Ouabain was administered, via subcutaneous osmotic pumps, to normal and adrenalectomized male Sprague-Dawley rats for 5 weeks. Blood pressure, plasma renin and aldosterone, and circulating and tissue levels of ouabain were determined. Results: Following a latent period, blood pressures and circulating ouabain were significantly elevated dose-dependently in glycoside-infused rats at 5 weeks. Upon withdrawal of the ouabain infusion, blood pressure and plasma ouabain levels normalized within 1 week. In rats that received 30 μg ouabain/kg per day, the circulating, kidney, hypothalamic and anterior pituitary levels of ouabain were increased significantly (by 7-, 15-, 2.8- and 2.1-fold, respectively), whereas the content of other tissues tested was unchanged. Blood pressure and plasma levels of ouabain correlated with hypothalamic and kidney glycoside content in the infused rats. High-performance liquid chromatography of the adrenal, renal, hypothalamic and pituitary extracts showed one major peak of ouabain immunoreactivity, with a retention time equivalent to that of commercial ouabain. Plasma renin activity was normal, whereas aldosterone levels were increased significantly to 2.9- and sevenfold in rats that received 10 and 30 μg ouabain/kg per day, respectively. Dietary salt loading suppressed aldosterone and did not exacerbate hypertension. In bilaterally adrenalectomized rats the ambient circulating and kidney levels of ouabain were low and ouabain infusion raised glycoside levels and blood pressure significantly. Conclusions: Prolonged infusion of ouabain in the normal rat raises the circulating, kidney, hypothalamic and anterior pituitary levels and induces a reversible hypertension with normal plasma renin activity. Although characterized by raised aldosterone levels, the hypertension does not require the adrenal glands and is not salt-sensitive. This model may be useful for exploring novel mechanisms of long-term regulation of blood pressure.

Original languageEnglish
Pages (from-to)549-560
Number of pages12
JournalJournal of Hypertension
Volume12
Issue number5
Publication statusPublished - 1994

Fingerprint

Ouabain
Blood Pressure
Hypertension
Aldosterone
Glycosides
Renin
Head Kidney
Salts
Kidney
Adrenal Glands
Sprague Dawley Rats

Keywords

  • Aldosterone
  • Cardiac glycosides
  • Circulation
  • Endogenous
  • Sodium pump

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Internal Medicine
  • Endocrinology

Cite this

Ouabain-induced hypertension in the rat : Relationships among plasma and tissue ouabain and blood pressure. / Manunta, Paolo; Rogowski, Amy C.; Hamilton, Bruce P.; Hamlyn, John M.

In: Journal of Hypertension, Vol. 12, No. 5, 1994, p. 549-560.

Research output: Contribution to journalArticle

Manunta, Paolo ; Rogowski, Amy C. ; Hamilton, Bruce P. ; Hamlyn, John M. / Ouabain-induced hypertension in the rat : Relationships among plasma and tissue ouabain and blood pressure. In: Journal of Hypertension. 1994 ; Vol. 12, No. 5. pp. 549-560.
@article{b06aa5bb59404bd4bbaed6434d8d82e9,
title = "Ouabain-induced hypertension in the rat: Relationships among plasma and tissue ouabain and blood pressure",
abstract = "Objectives: To determine the steady-state dose-dependence of blood pressure, plasma and tissue ouabain during continuous infusion of ouabain in the rat, and to evaluate the adrenal dependence and effect of a high salt intake on this form of hypertension. Design and methods: Ouabain was administered, via subcutaneous osmotic pumps, to normal and adrenalectomized male Sprague-Dawley rats for 5 weeks. Blood pressure, plasma renin and aldosterone, and circulating and tissue levels of ouabain were determined. Results: Following a latent period, blood pressures and circulating ouabain were significantly elevated dose-dependently in glycoside-infused rats at 5 weeks. Upon withdrawal of the ouabain infusion, blood pressure and plasma ouabain levels normalized within 1 week. In rats that received 30 μg ouabain/kg per day, the circulating, kidney, hypothalamic and anterior pituitary levels of ouabain were increased significantly (by 7-, 15-, 2.8- and 2.1-fold, respectively), whereas the content of other tissues tested was unchanged. Blood pressure and plasma levels of ouabain correlated with hypothalamic and kidney glycoside content in the infused rats. High-performance liquid chromatography of the adrenal, renal, hypothalamic and pituitary extracts showed one major peak of ouabain immunoreactivity, with a retention time equivalent to that of commercial ouabain. Plasma renin activity was normal, whereas aldosterone levels were increased significantly to 2.9- and sevenfold in rats that received 10 and 30 μg ouabain/kg per day, respectively. Dietary salt loading suppressed aldosterone and did not exacerbate hypertension. In bilaterally adrenalectomized rats the ambient circulating and kidney levels of ouabain were low and ouabain infusion raised glycoside levels and blood pressure significantly. Conclusions: Prolonged infusion of ouabain in the normal rat raises the circulating, kidney, hypothalamic and anterior pituitary levels and induces a reversible hypertension with normal plasma renin activity. Although characterized by raised aldosterone levels, the hypertension does not require the adrenal glands and is not salt-sensitive. This model may be useful for exploring novel mechanisms of long-term regulation of blood pressure.",
keywords = "Aldosterone, Cardiac glycosides, Circulation, Endogenous, Sodium pump",
author = "Paolo Manunta and Rogowski, {Amy C.} and Hamilton, {Bruce P.} and Hamlyn, {John M.}",
year = "1994",
language = "English",
volume = "12",
pages = "549--560",
journal = "Journal of Hypertension",
issn = "0263-6352",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Ouabain-induced hypertension in the rat

T2 - Relationships among plasma and tissue ouabain and blood pressure

AU - Manunta, Paolo

AU - Rogowski, Amy C.

AU - Hamilton, Bruce P.

AU - Hamlyn, John M.

PY - 1994

Y1 - 1994

N2 - Objectives: To determine the steady-state dose-dependence of blood pressure, plasma and tissue ouabain during continuous infusion of ouabain in the rat, and to evaluate the adrenal dependence and effect of a high salt intake on this form of hypertension. Design and methods: Ouabain was administered, via subcutaneous osmotic pumps, to normal and adrenalectomized male Sprague-Dawley rats for 5 weeks. Blood pressure, plasma renin and aldosterone, and circulating and tissue levels of ouabain were determined. Results: Following a latent period, blood pressures and circulating ouabain were significantly elevated dose-dependently in glycoside-infused rats at 5 weeks. Upon withdrawal of the ouabain infusion, blood pressure and plasma ouabain levels normalized within 1 week. In rats that received 30 μg ouabain/kg per day, the circulating, kidney, hypothalamic and anterior pituitary levels of ouabain were increased significantly (by 7-, 15-, 2.8- and 2.1-fold, respectively), whereas the content of other tissues tested was unchanged. Blood pressure and plasma levels of ouabain correlated with hypothalamic and kidney glycoside content in the infused rats. High-performance liquid chromatography of the adrenal, renal, hypothalamic and pituitary extracts showed one major peak of ouabain immunoreactivity, with a retention time equivalent to that of commercial ouabain. Plasma renin activity was normal, whereas aldosterone levels were increased significantly to 2.9- and sevenfold in rats that received 10 and 30 μg ouabain/kg per day, respectively. Dietary salt loading suppressed aldosterone and did not exacerbate hypertension. In bilaterally adrenalectomized rats the ambient circulating and kidney levels of ouabain were low and ouabain infusion raised glycoside levels and blood pressure significantly. Conclusions: Prolonged infusion of ouabain in the normal rat raises the circulating, kidney, hypothalamic and anterior pituitary levels and induces a reversible hypertension with normal plasma renin activity. Although characterized by raised aldosterone levels, the hypertension does not require the adrenal glands and is not salt-sensitive. This model may be useful for exploring novel mechanisms of long-term regulation of blood pressure.

AB - Objectives: To determine the steady-state dose-dependence of blood pressure, plasma and tissue ouabain during continuous infusion of ouabain in the rat, and to evaluate the adrenal dependence and effect of a high salt intake on this form of hypertension. Design and methods: Ouabain was administered, via subcutaneous osmotic pumps, to normal and adrenalectomized male Sprague-Dawley rats for 5 weeks. Blood pressure, plasma renin and aldosterone, and circulating and tissue levels of ouabain were determined. Results: Following a latent period, blood pressures and circulating ouabain were significantly elevated dose-dependently in glycoside-infused rats at 5 weeks. Upon withdrawal of the ouabain infusion, blood pressure and plasma ouabain levels normalized within 1 week. In rats that received 30 μg ouabain/kg per day, the circulating, kidney, hypothalamic and anterior pituitary levels of ouabain were increased significantly (by 7-, 15-, 2.8- and 2.1-fold, respectively), whereas the content of other tissues tested was unchanged. Blood pressure and plasma levels of ouabain correlated with hypothalamic and kidney glycoside content in the infused rats. High-performance liquid chromatography of the adrenal, renal, hypothalamic and pituitary extracts showed one major peak of ouabain immunoreactivity, with a retention time equivalent to that of commercial ouabain. Plasma renin activity was normal, whereas aldosterone levels were increased significantly to 2.9- and sevenfold in rats that received 10 and 30 μg ouabain/kg per day, respectively. Dietary salt loading suppressed aldosterone and did not exacerbate hypertension. In bilaterally adrenalectomized rats the ambient circulating and kidney levels of ouabain were low and ouabain infusion raised glycoside levels and blood pressure significantly. Conclusions: Prolonged infusion of ouabain in the normal rat raises the circulating, kidney, hypothalamic and anterior pituitary levels and induces a reversible hypertension with normal plasma renin activity. Although characterized by raised aldosterone levels, the hypertension does not require the adrenal glands and is not salt-sensitive. This model may be useful for exploring novel mechanisms of long-term regulation of blood pressure.

KW - Aldosterone

KW - Cardiac glycosides

KW - Circulation

KW - Endogenous

KW - Sodium pump

UR - http://www.scopus.com/inward/record.url?scp=0028271160&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028271160&partnerID=8YFLogxK

M3 - Article

C2 - 7930555

AN - SCOPUS:0028271160

VL - 12

SP - 549

EP - 560

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 5

ER -