The current concept for the cardiac glycoside receptor

Bodemann, H. H.

doi:10.1002/clc.4960040502

Cited by 6 publications

(1 citation statement)

References 32 publications

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“…Nanomolar ouabain, however, augments myogenic constriction in rodent isolated arteries [36, 42, 65, 165, 166]. The first experimental evidence of a previously-unrecognized cardenolide structure-activity relationship was the observation that the prolonged administration of digoxin, also an Na,K-ATPase inhibitor [167], does not raise BP in normal rats, whereas ouabain does (Fig. 2) [168].…”

Section: Cardiotonic Steroid Structure-activity Relationships: Hypmentioning

confidence: 99%

Signaling mechanisms that link salt retention to hypertension: Endogenous ouabain, the Na+ pump, the Na+/Ca2+ exchanger and TRPC proteins

Blaustein

Hamlyn

2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Salt retention as a result of chronic, excessive dietary salt intake, is widely accepted as one of the most common causes of hypertension. In a small minority of cases, enhanced Na+ reabsorption by the kidney can be traced to specific genetic defects of salt transport, or pathological conditions of the kidney, adrenal cortex, or pituitary. Far more frequently, however, the salt retention may be the result of minor renal injury or small genetic variation in renal salt transport mechanisms. How the salt retention actually leads to the increase in peripheral vascular resistance (the hallmark of hypertension) and the elevation of blood pressure remain an enigma. Here we review the evidence that endogenous ouabain (an adrenocortical hormone), arterial smooth muscle α2 Na+ pumps, type-1 Na/Ca exchangers, and receptor- and store-operated Ca2+ channels play key roles in the pathway that links salt to hypertension. We discuss cardenolide structure-function relationships in an effort to understand why prolonged administration of ouabain, but not digoxin, induces hypertension, and why digoxin is actually anti-hypertensive. Finally, we summarize recent observations which indicate that ouabain upregulates arterial myocyte Ca2+ signaling mechanisms that promote vasoconstriction, while simultaneously downregulating endothelial vasodilator mechanisms. In sum, the reports reviewed here provide novel insight into the molecular mechanisms by which salt retention leads to hypertension.

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Section: Cardiotonic Steroid Structure-activity Relationships: Hypmentioning

confidence: 99%

Signaling mechanisms that link salt retention to hypertension: Endogenous ouabain, the Na+ pump, the Na+/Ca2+ exchanger and TRPC proteins

Blaustein

Hamlyn

2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Agents for the treatment of heart failure

Bristol¹,

Evans²

1983

Medicinal Research Reviews

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Sequestration of cardenolides inOncopeltus fasciatus: Morphological and physiological adaptations

1986

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The morphological and physiological adaptations associated with sequestration of cardenolides by the lygaeidOncopeltus fasciatus are summarized and discussed. Cardenolides are efficiently accumulated inO. fasciatus; however, the insect does not appear to suffer any physiological cost as a result of handling large amounts of these plant toxins. Morphological adaptations of the insect include a modified integument composed of a double layered epidermis with an inner layer (the dorsolateral space) specialized for cardenolide storage. Special weak areas of the cuticle are found on both the thorax and abdomen, which rupture when the insect is squeezed, resulting in the cardenolide-rich contents of the inner epidermal layer being released onto the body surface in the form of discrete spherical droplets. Physiological adaptations include selective sequestration of food plant cardenolides, concentration of cardenolides in the dorsolateral space, passive uptake of cardenolides at the gut and dorsolateral space requiring little energy output, reabsorption of secreted cardenolides by the Malpighian tubules, high in vivo tolerance to cardenolides, and the presence of cardenolide-resistant Na,K-ATPases.

show abstract

The current concept for the cardiac glycoside receptor

Cited by 6 publications

References 32 publications

Signaling mechanisms that link salt retention to hypertension: Endogenous ouabain, the Na+ pump, the Na+/Ca2+ exchanger and TRPC proteins

Signaling mechanisms that link salt retention to hypertension: Endogenous ouabain, the Na+ pump, the Na+/Ca2+ exchanger and TRPC proteins

Agents for the treatment of heart failure

Sequestration of cardenolides inOncopeltus fasciatus: Morphological and physiological adaptations

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