Effects of Ouabain on Blood Pressure Regulation in Rats

Yasujima, Minoru; Abe, Keishi; Tanno, Masaya; Kohzuki, Masahiro; Kasai, Yutaka; Sato, Makito; Omata, Ken; Takeuchi, Kazuhisa; Yoshinaga, Kaoru; Masugi, Fuminori; Ogihara, Toshio

doi:10.1097/00004872-198610000-00012

Cited by 26 publications

(13 citation statements)

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“…Differences in the experimental protocols can explain these different results. First, in the study by Yasujima et al 13 BP was measured for only 2 to 6 days after the initiation of intravenous ouabain infusion. Sekihara et al 12 injected ouabain only once a week.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, pressor responses to norepinephrine were enhanced by low doses of ouabain 18 but attenuated by high doses. 13 The mechanisms responsible for chronic ouabaininduced hypertension in normotensive rats are not yet clear. Ouabain-induced hypertension was associated with an increase in TPR, 15 and it was postulated 15 that an inhibition of Na + ,K + -ATPase in vascular smooth muscle cells is responsible for the TPR increase.…”

Section: Discussionmentioning

confidence: 99%

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Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats.

Huang

Harmsen

et al. 1994

Hypertension

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To assess whether chronic ouabain administration causes hypertension by increasing sympathetic activity, we recorded arterial blood pressure and heart rate at rest and after ganglionic blockade in conscious Wistar rats following 10 to 14 days of central or peripheral administration of ouabain. Intracerebroventricular or intravenous infusion of ouabain (10 fig/d for both) as well as subcutaneous ouabain pellets (releasing 25 fig ouabain/d per pellet) increased mean arterial pressure by 20 to 30 mm Hg and heart rate by 40 to 60 beats per minute. Ouabain pellets increased blood pressure and heart rate in a dose-related manner. After 2 weeks of all ouabain treatments, ouabainlike activity in plasma was not changed but increased significantly in hypothalamus and adrenals. Ouabainlike activity in the adrenals was increased more T he relation between high sodium intake and hypertension in salt-sensitive hypertensive rats is complex and not yet understood. We have postulated that high sodium intake intermittently increases Na + concentrations in the cerebrospinal fluid, inducing increased central levels of ouabainlike activity (OLA) and thereby an increase in sympathetic outflow and blood pressure (BP).1 ' 2 Substances with OLA are present peripherally and centrally in both normotensive and hypertensive humans and animals 2 -4 and may be of central origin.2 -4 Brain OLA content is higher in spontaneously hypertensive rats (SHR) than Wistar-Kyoto (WKY) rats, and high sodium intake further increases brain OLA in SHR. 4 Augmented sympathetic activity has been documented in several forms of sodiumdependent hypertension, including Dahl salt-sensitive (DS) rats 5 and SHR. 6 Brain OLA may play a primary role in mediating the sympathoexcitatory and hypertensive effects of high sodium intake in SHR 7 and DS rats. In humans, circulating OLA is indistinguishable from the glycoside ouabain in terms of biochemical structure and several physiological effects.3 Furthermore, receptors for ouabain in, for instance, arterial smooth muscle cells 9 and the central nervous system 10 appear to be identical to those for OLA. If an increase in brain or peripheral OLA contributes to the development of hypertension in sodium-sensitive rats, chronic administration of exogenous ouabain should induce hypertension in normotensive rats as well. In normotensive rats, From the Hypertension Unit, University of Ottawa (Ontario, Canada) Heart Institute.Correspondence to Frans H.H. Leenen, MD, PhD, FRCPC, Hypertension Unit, Room H360, University of Ottawa Heart Institute, 40 Ruskin St, Ottawa, Ontario, Canada K1Y 4E9. by intravenous than subcutaneous or intracerebroventricular ouabain treatment, but the different treatment modes caused similar increases in the hypothalamus. Concomitant central infusion of antibody Fab fragments against ouabain prevented the ouabain pellet-induced increases in blood pressure and heart rate. Ganglionic blockade by intravenous hexamethonium normalized blood pressure and heart rate in ouabaintreated rats. These data s...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats.

Huang

Harmsen

et al. 1994

Hypertension

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“…In addition, we also assumed that digoxin at the dose employed, attained effective levels to inhibit Nat, K+-ATPase, since the plasma levels of digoxin attained in the present experiments was approximately 1,000 fold more than those in digitalized man (1-3 ng/ml). The antihypertensive effect of ouabain, in rats made hypertensive by NE has been previously reported from our laboratory (Yasujima et al 1986b). Based on the previous and present findings, it is reasonable to assume that the attenuation by cardiac glycosides of the blood pressure elevation induced by chronic infusion of NE may be generalized to all cardiac glycosides.…”

Section: Discussionmentioning

confidence: 67%

“…However, we have previously demonstrated that chronic administration of ouabain, a cardiac glycoside, failed to induce any significant changes in blood pressure and sodium excretion in rats (Yasujima et al 1986b). On the contrary, continuous infusion of ouabain was effective in counteracting the hypertensive action of norepinephrine (NE) infused chronically (Yasujima et al 1986b).…”

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confidence: 95%

Effects of digoxin on blood pressure responses to norepinephrine, angiotensin II and vasopressin in conscious rats.

Yasujima

Abe

Tanno

et al. 1990

Tohoku J. Exp. Med.

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“…[3][4][5][6] Other studies, however, have failed to demonstrate a hypertensive effect of ouabain in rats, [7][8][9] sheep, 10 dogs, 11 and humans. 12 The diverging results in rats could be linked to differences in the doses and duration of ouabain administration in the strains used or in the methods used for blood pressure measurement.…”

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confidence: 99%

Regulation of Blood Pressure During Long-Term Ouabain Infusion in Long-Evans Rats

WANG¹

1999

American Journal of Hypertension

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Effects of Ouabain on Blood Pressure Regulation in Rats

Cited by 26 publications

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Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats.

Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats.

Effects of digoxin on blood pressure responses to norepinephrine, angiotensin II and vasopressin in conscious rats.

Regulation of Blood Pressure During Long-Term Ouabain Infusion in Long-Evans Rats

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