Modulation of the levels of ouabain‐like compound by central catecholamine neurons in rats

Yamada, Kaoru; Goto, Atsuo; Omata, Masao

doi:10.1016/0014-5793(95)00078-n

Cited by 20 publications

(13 citation statements)

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“…Correlations were found between OLC and plasma concentrations of lactate, norepinephrine, as well as heart rate and systolic blood pressure. Such correlations were also seen under stress 9,26,27 and when ouabain was infused intraventricularly to rats. 28 These correlations may be causative, but they may also be purely coincidental.…”

Section: Discussionmentioning

confidence: 61%

Ouabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs

et al. 2005

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Abstract-Ouabain, an inhibitor of the sodium pump, has been identified as a constituent of bovine adrenal glands. We were interested whether the release of this cardiotonic steroid is stimulated by physical exercise. Hence, athletes and healthy dogs were subjected to ergometry. Ouabain-like compound (OLC) was measured in venous blood by enzyme-linked immunosorbent assay as well as by 86 Rb ϩ uptake inhibition (as ouabain equivalents). OLC increased in venous blood of athletes after 15 minutes of ergometry from 2.5Ϯ0.5 to 86.0Ϯ27.2 nmol/L (nϭ51; PϽ0.001), as did the concentration of a circulating inhibitor of the sodium pump from 7.3Ϯ1.7 to 129.8Ϯ51 nmol/L (ouabain equivalents, PϽ0.05). Half-maximal increase in heart rate and systolic blood pressure occurred at 5.1Ϯ1.2 nmol/L and at 30Ϯ1 nmol/L OLC, respectively. On rest, OLC decreased in humans and dogs with a half-life of 3 to 5 minutes. In beagles exposed to moderate exercise on a treadmill for 13 minutes, levels of OLC increased 46-fold (from 3.7Ϯ0.8 to 166.9Ϯ91.8 nmol/L; nϭ6; PϽ0.005). This effect was suppressed when the dogs had been treated for 3 weeks with the ␤ 1 -adrenergic receptor blocker atenolol or the angiotensin-converting enzyme inhibitor benazepril. We conclude that OLC changes rapidly during exercise and is under the control of norepinephrine and angiotensin II. Key Words: angiotensin-converting enzyme inhibitor Ⅲ ␤-blocker Ⅲ circulation Ⅲ endogenous ouabain Ⅲ hypertension Ⅲ sodium pump hypertension O uabain or its isomer has been isolated from blood, adrenals, and hypothalamus 1-3 as one of the endogenous cardiac glycosides circulating in blood plasma. 4 Evidently, ouabain is synthesized in adrenal glands, 1,5,6 but it may also be accumulated there after resorption from the gut. 7 Bovine adrenocortical cells in tissue culture release ouabain on exposure to epinephrine, angiotensin II, or corticotropin. 1,6,8 Whether this in vitro finding translates into the in vivo situation is unclear. If so, physical exercise associated with the increase in epinephrine and norepinephrine should consequently increase endogenous ouabain. Previous studies showed ambiguous results. An increase 9 as well as a decrease of plasma concentrations of ouabain-like compounds (OLCs) 10,11 have been reported. Here, we investigated the effect of physical exercise on the endogenous ouabain plasma concentration in several experimental settings as well as the influence of ␤-blockade and angiotensin-converting enzyme (ACE) inhibition. Materials and MethodsAll chemicals were of the highest purity available. Anti-ouabain antibodies from sheep (CN2710) were from B.R.A.H.M.S. Arzneimittel (Dr A. Bergmann), Henningsdorf, Germany. The antibodies showed cross-reactivities with k-strophanthin 42%, ouabagenin 27%, dihydro-ouabain 0.3%, digitoxin 0.07%, and proscillaridin (Ͻ0.1%), and no cross-reaction (Ͻ0.01%) with strophanthidin, digoxin, digitoxigenin, oleandrin, marinobufagin, bufalin, cinobufagin, cinobufotalin, and 19 other steroid hormones. Human Patients and ControlsWritten inf...

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Section: Discussionmentioning

confidence: 61%

Ouabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs

et al. 2005

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“…This could be the rationale for colocalization of high ouabain affinity Na ϩ pumps and Na ϩ ͞Ca 2ϩ exchangers in these PM areas. This might reveal how an endogenous ouabain isomer (12,(37)(38)(39), which circulates at nanomolar concentrations (40) and is present in the brain (38,39), could, by modulating the activity of these high ouabain affinity Na ϩ pumps (28,37), play a role in many physiological, and even pathophysiological, processes (12). Finally, this may also explain why the isoformspecific features of the ouabain binding regions of ␣2 and ␣3 have been so well conserved during the evolution of higher animals (4,10).…”

Section: Resultsmentioning

confidence: 99%

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Juhaszova

Blaustein

1997

Proc. Natl. Acad. Sci. U.S.A.

280

246

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Three isoforms (␣1, ␣2, and ␣3) of the catalytic (␣) subunit of the plasma membrane (PM) Na ؉ pump have been identified in the tissues of birds and mammals. These isoforms differ in their affinities for ions and for the Na ؉ pump inhibitor, ouabain. In the rat, ␣1 has an unusually low affinity for ouabain. The PM of most rat cells contains both low (␣1) and high (␣2 or ␣3) ouabain affinity isoforms, but precise localization of specific isoforms, and their functional significance, are unknown. We employed high resolution immunocytochemical techniques to localize ␣ subunit isoforms in primary cultured rat astrocytes, neurons, and arterial myocytes. Isoform ␣1 was ubiquitously distributed over the surfaces of these cells. In contrast, high ouabain affinity isoforms (␣2 in astrocytes, ␣3 in neurons and myocytes) were confined to a reticular distribution within the PM that paralleled underlying endoplasmic or sarcoplasmic reticulum. This distribution is identical to that of the PM Na͞Ca exchanger. This raises the possibility that ␣1 may regulate bulk cytosolic Na ؉ , whereas ␣2 and ␣3 may regulate Na ؉ and, indirectly, Ca 2؉ in a restricted cytosolic space between the PM and reticulum. The high ouabain affinity Na ؉ pumps may thereby modulate reticulum Ca 2؉ content and Ca 2؉ signaling.

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“…Several mechanisms may mediate these effects of central Ang II on plasma aldosterone and corticosterone levels. Intracerebroventricular-infused Ang II may enhance EO release from the pituitary and adrenal, 31 and plasma EO may increase aldosterone production and secretion. 32 Because plasma corticosterone also clearly increases, Ang II-induced adrenocorticotropic hormone (ACTH) release may also contribute.…”

Section: Discussionmentioning

confidence: 99%

Role of Brain Corticosterone and Aldosterone in Central Angiotensin II–Induced Hypertension

et al. 2013

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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.

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Modulation of the levels of ouabain‐like compound by central catecholamine neurons in rats

Cited by 20 publications

References 19 publications

Ouabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs

Ouabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Role of Brain Corticosterone and Aldosterone in Central Angiotensin II–Induced Hypertension

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Modulation of the levels of ouabain‐like compound by central catecholamine neurons in rats

Cited by 20 publications

References 19 publications

Ouabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs

Ouabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs

Na + pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Role of Brain Corticosterone and Aldosterone in Central Angiotensin II–Induced Hypertension

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Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells