Chemistry and Structure-Activity Relationships of Cardioactive Steroids

Güntert, Theodor W.; Linde, Horst H. A.

doi:10.1007/978-3-642-68163-9_2

Cited by 8 publications

(2 citation statements)

References 47 publications

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“…a steroid nucleus with a lactone ring at C-17 and a hydroxyl group at C-14. The 5-membered-and 6-memberedlactone rings, in cardenolides and bufadienolides, respectively, are considered the most essential functional group of these substances (Guntert and Linde, 1981). The endogenous DLC are either cardenolides or bufadienolides (Fig.…”

Section: Identification Of Endogenous Dlcmentioning

confidence: 99%

The digitalis-like steroid hormones: New mechanisms of action and biological significance

Nesher¹,

Shpolansky²,

et al. 2007

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Section: Identification Of Endogenous Dlcmentioning

confidence: 99%

The digitalis-like steroid hormones: New mechanisms of action and biological significance

Nesher¹,

Shpolansky²,

et al. 2007

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“…Certain steroids with trans-trans-cis ring fusions are cardiotonic [154, 155], while those with cis-trans-trans ring fusions (e.g., common bile salts, 14α-digitoxigenin and 14α-artebufogenin) are either inactive or very weak [156, 157]. Addition of one or more sugars to the cardenolide steroid nucleus increases the potency, while inversion of the lactone configuration at C17 from β to α [158], or saturation (e.g., dihydroouabain and dihydrodigoxin) of the lactone ring, reduces the cardiotonic activity 10-30 fold. These fundamental relationships, obtained with cardiac preparations, have been widely assumed to be valid in other physiological systems.…”

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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Digitalis Research in Berlin–Buch—Retrospective and Perspective Views

Repke¹,

Megges²,

Weiland³

et al. 1995

Angew. Chem. Int. Ed. Engl.

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“The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.” These declarations, which stem from the famous book “An Account of the Foxglove and some of its Medical Uses” by physician William Withering in 1785 in which he introduced preparations from digitalis leaves in the therapy of dropsy (cardiac failure), are cited here by the senior author because of his awareness of the difficulties in presenting a balanced report on his life‐long research project on the further development of digitalis. His decision to devote himself to digitalis research originated at the bedside, when as a physician he experienced the grim final stages of cardiac failure in which no real help for the patients is possible. Unfortunately, his research project did not fit into the research program decreed by the Ministry of Science of the German Democratic Republic, so that he was ordered to stop the digitalis project in favor of biomembrane studies. Fortunately, he got round the ban simply by labeling the digitalis‐like acting steroids as probes for the cell membrane‐located Na+/K+‐transporting ATPase which he had just recognized as the digitalis target (receptor) enzyme. These and other ventures by the authors are collated here for the first time. The aim of this review is to foster straightforward research for solving a major challenge: the development of steroidal drugs for the prevention and cure of cardiac failure.

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Chemistry and Structure-Activity Relationships of Cardioactive Steroids

Cited by 8 publications

References 47 publications

The digitalis-like steroid hormones: New mechanisms of action and biological significance

The digitalis-like steroid hormones: New mechanisms of action and biological significance

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

Digitalis Research in Berlin–Buch—Retrospective and Perspective Views

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