Endogenous ouabain, sodium balance and blood pressure: a review and a hypothesis

Hamlyn, John M.; Hamilton, Bruce P.; Manunta, Paolo

doi:10.1097/00004872-199602000-00002

Cited by 173 publications

(121 citation statements)

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“…NKA activity permits the creation and the maintenance of Na ϩ and K ϩ gradients across cell membranes that are essential for both cellular and body ion homeostasis. In addition to this functional role, NKA plays a role as a receptor for cardiac glycosides widely used in the treatment of heart failure because of their positive ionotropic action (1) and presumably for endogenous digitalis-like compounds identified in mammals (2). The minimal functional unit of NKA comprises a catalytic ␣ subunit containing the cation, ATP and phosphate binding sites, and a glycosylated ␤ subunit required for the correct folding and functional maturation of the ␣ subunit (3).…”

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confidence: 99%

Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties

Crambert

Füzesi

Garty

et al. 2002

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

253

285

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A family of small, single-span membrane proteins (the FXYD family) has recently been defined based on their sequence and structural homology. Some members of this family have already been identified as tissue-specific regulators of Na,K-ATPase (NKA). In the present study, we demonstrate that phospholemman (PLM) (FXYD1), so far considered to be a heart-and muscle-specific channel or channel-regulating protein, associates specifically and stably with six different ␣-␤ isozymes of NKA after coexpression in Xenopus oocytes, and with ␣1-␤, and less efficiently with ␣2-␤ isozymes, in native cardiac and skeletal muscles. Stoichiometric association of PLM with NKA occurs posttranslationally either in the Golgi or the plasma membrane. Interaction of PLM with NKA induces a small decrease in the external K ؉ affinity of ␣1-␤1 and ␣2-␤1 isozymes and a nearly 2-fold decrease in the internal Na ؉ affinity. In conclusion, this study demonstrates that PLM is a tissue-specific regulator of NKA that may play an essential role in muscle contractility.

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mentioning

confidence: 99%

Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties

Crambert

Füzesi

Garty

et al. 2002

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

253

285

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“…These results suggest that ouabain-induced hypertension is accompanied by increased NO release derived from endothelial NOS and neuronal NOS and increased release of an endothelial hyperpolarizing factor that presumably opens K Ca, all of which contribute to the increased negative modulation of the phenylephrine contraction. nitric oxide; endothelial-dependent hyperpolarizing factor; phenylephrine THE PLASMA LEVELS of an endogenous circulating Na ϩ -K ϩ -ATPase inhibitor, characterized as ouabain or a closely related compound (17,36), are increased in several animal models of hypertension (19,39), as well as in human essential hypertension (20). Several studies have shown that chronic administration of ouabain induces hypertension, an effect that seems to be linked to the inhibition of the Na ϩ -K ϩ -ATPase (10,22,23,45,54), although sodium pump inhibition seems not to be the exclusive mechanism of the ouabain-hypertensive effect (26,31,32,52).…”

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confidence: 99%

Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors

Rossoni

Salaíces

Miguel

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors. Am J Physiol Heart Circ Physiol 283: H2110-H2118, 2002. First published July 11, 2002 10.1152/ajpheart.00454.2002The involvement of nitric oxide (NO), prostaglandins, and calcium-dependent potassium channel (K Ca) activators on the negative modulation of phenylephrine-induced contractions was evaluated on the isolated aorta and caudal (CAU) artery obtained from rats treated with ouabain for 5 wk to induce hypertension. In ouabain-treated rats, the reactivity to phenylephrine was reduced in the endothelium-intact aorta but not the CAU segments. Endothelial modulation of phenylephrine contraction, as demonstrated by endothelium removal, NO synthase (NOS) inhibition with N -nitro-L-arginine methyl ester and aminoguanidine, as well as K Ca inhibition with tetraethylammonium, was more pronounced in segments from ouabain-treated animals, and here greater effects were seen in the aorta than in CAU. An increased expression of endothelial NOS and neuronal NOS was seen in the aorta after ouabain treatment. In CAU, only endothelial NOS was detected and ouabain treatment did not alter its expression. These results suggest that ouabain-induced hypertension is accompanied by increased NO release derived from endothelial NOS and neuronal NOS and increased release of an endothelial hyperpolarizing factor that presumably opens K Ca, all of which contribute to the increased negative modulation of the phenylephrine contraction. nitric oxide; endothelial-dependent hyperpolarizing factor; phenylephrine THE PLASMA LEVELS of an endogenous circulating Na ϩ -K ϩ -ATPase inhibitor, characterized as ouabain or a closely related compound (17,36), are increased in several animal models of hypertension (19,39), as well as in human essential hypertension (20). Several studies have shown that chronic administration of ouabain induces hypertension, an effect that seems to be linked to the inhibition of the Na ϩ -K ϩ -ATPase (10,22,23,45,54), although sodium pump inhibition seems not to be the exclusive mechanism of the ouabain-hypertensive effect (26,31,32,52). This enzyme is found in most eukaryotic cells and is the main system involved in the maintenance of sodium homeostasis and the membrane potential, essential factors for controlling vascular tone and blood pressure. It has been suggested that alterations in the activity of the sodium pump might be involved in the genesis or maintenance of hypertensive states (3, 33). Additionally, the hypertension induced by ouabain treatment has been associated with actions in the central nervous system that increase sympathetic activity by activation of the central renin-angiotensin system and impair the arterial baroreceptor reflex (22, 23) and associated with actions in the periphery that produce changes in responsiveness to contractile agents (10,26,45).In some isolated vascular preparations, acutely administered ouabain, at nanomolar concentrations, can enhance the actions of phenylephrine (43). Higher mi...

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“…Diyetle sodyum alımı arttığı zaman susama ve antidiüretik hormon feedback sistemleri aktive olur ve böylece plazma sodyum konsantrasyonu ve osmolalitesi sabit tutulmaya çalı-şılır. Sodyum yüklenmesinin, Na / K ATP' az pompasını inhibe ettiği, bunun ise intrasellüler sodyum ve kalsiyum konsantrasyonunun artışına ve hipertansiyona yol açtığı bildirilmiştir (21).…”

Section: Sdby' De Sodyum Yükünün Hipertansiyona Etkisiunclassified

The pathogenesis of hypertension in end stage renal disease; the importance of the sodium and volume control

Tekçe¹,

Aktas²,

Kürşat³

2012

Turk J Bioch

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Hipertansiyon, son dönem böbrek yetmezliği (SDBY) hastalarında oldukça yaygın görülen bir klinik problemdir. Buna karşın bu hastaların etkin kan basıncı kontrolünden çoğu zaman uzak olmasının önemli bir sebebi, bu hasta grubunda hipertansiyon fizyopatolojisinin karmaşık, multifaktoriyel ve az anlaşılmış olmasından kaynaklanmaktadır. Hemodiyaliz hastalarındaki hipertansiyonun patogenezinde majör risk faktörlerinden ikisi, artmış ekstrasellüler volüm ve sodyum alımıdır. Buradan yola çıkarak terapödik hedefin anahatları da bu etyopatogenez çerçevesinde belirlenmelidir. Bulgular SDBY hastalarında sodyum yüklenmesinin, volüm yüklenmesi ve hipertansiyonla paralel seyrettiğini düşündürmektedir. Bu durum sodyumun, hipertansiyon için kilit bir rol oynadığını ve tedavinin yönetiminde esas uğraşı alanının antihipertansif ilaç desteği değil, tuz kısıtlaması ve gereğinde ek ultrafiltrasyon desteğinin olması yönündeki mücadelenin merkezi rolünü düşündürmektedir.Hypertension is a common clinical problem among patients with end stage renal failure. Because physiopathology of hypertension in these patients is multifactorial, complicated and less understood, effective blood pressure control usually cannot be achieved in this population. Major two risk factors in the pathogenesis of hypertension in patients receiving hemodialysis treatment are extracellular volume and dietary sodium intake. Therapeutic targets should be determined according to etiopathogenesis. There is increasing number of evidence indicating sodium intake in patients with end stage renal failure is related to volume overload and hypertension. Because sodium plays a key role in hypertension development among these population, salt restriction and additional ultrafiltration, if necessary, should be the mainstay of the antihypertensive treatment instead of antihypertensive drugs.Anahtar Kelimeler: Son dönem böbrek yetmezliği, hipervolemi, sodyum. Keywords:End stage renal disease, hypervolemia, sodium. Son dönem böbrek yetmezliğinde hipertansiyonHipertansiyon, son dönem böbrek yetmezliği (SDBY) hastalarında oldukça yaygın olarak görü-len en önemli klinik problemlerden birisidir. Bu popülasyonda ölümlerin önde gelen nedeni kardiyovasküler hastalıklardır (% 50-70) ve hipertansiyon, kardiyovasküler komplikasyonlar için anlamlı bir risk faktörüdür (1). Yapılan çeşitli epidemiyolojik çalışmalarda, hemodiyaliz hastalarındaki hipertansiyon oranının % 70 ile % 90 arasında değiştiği bildirilmektedir (2).1238 kronik hemodiyaliz hastası ile yapılan geniş bir kesitsel çalışmada, olguların diyaliz öncesi sistolik kan basıncı ortalaması 152 ± 25 mm Hg olarak saptanmıştır (3). JNC VII raporunda bildirilen normal değerler göz önünde bulundurulduğunda, bu hastaların %30' undan daha azında normal kabul edilebilecek kan basıncı değerleri mevcuttur. Hipertansiyonun, son dönem böbrek yetmezliğinde artmış mortalite ve morbidite için bağımsız bir risk faktörü olduğu bilinmektedir (4). Buna karşın bu hasta grubu, etkin kan basıncı kontrolünden çoğu zaman yoksundur ve kontrolsüz hip...

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Endogenous ouabain, sodium balance and blood pressure: a review and a hypothesis

Cited by 173 publications

References 0 publications

Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties

Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties

Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors

The pathogenesis of hypertension in end stage renal disease; the importance of the sodium and volume control

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