A COMPARISON OF THE DIRECT PERIPHERAL ACTIONS UPON SYSTEMIC VENOUS PRESSURE OF <i>k</i>‐STROPHANTHOSID, DIGOXIN AND OUABAIN

Jh, Tyrer

doi:10.1113/expphysiol.1953.sp001025

Cited by 4 publications

(2 citation statements)

References 8 publications

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“…Although previous studies on isolated vascular strips (1-4), on the perfused hind limb of the dog (5,22), and on the total systemic circulation of dogs, sheep, and humans on cardiopulmonary bypass (5,6,8,23) indicate that digitalis glycosides constrict vascular smooth muscle, the conditions under which these experiments were carried out were grossly abnormal, and the relevance of' the data to,intact, unanesthetized, normal man may be questioned. The present.…”

Section: Discussionmentioning

confidence: 83%

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Mason¹,

Braunwald²,

Karsh³

et al. 1964

J. Clin. Invest.

304

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Although the therapeutic action of digitalis is generally agreed to result largely from its ability to stimulate the contraction of the myocardium, there has been considerable suspicion that cardiac glycosides may also act directly upon the systemic vascular bed. Excised arterial and venous strips contract when exposed to digitalis glycosides (1-4), and generalized systemic arteriolar and venous constriction has been induced by digitalis in-anesthetized open-chest dogs on cardiopulmonary bypass (5, 6). In normal human subjects digitalis glycosides elevate arterial pressure and either have little effect on or diminish cardiac output, thus augmenting the calculated systemic vascular resistance (7). More direct evidence that digitalis acts upon vascular smiiooth muscle was provided by the observation that the drug elevated systemic vascular resistance in patients on total cardiopulmonary bypass, in whom the systemic perfusion rate was held constant, and in whom the cardiac effects of the drug could not influence arterial pressure directly (8). Little information is available, however, concerning the extracardiac actions of digitalis glycosides when given in the usual clinical doses to intact human subjects. The present investigation was undertaken to characterize the effects of ouabain on a specific vascular bed, that of the forearm. The effects of the drug on both the resistance and capacitance vessels were examined in normal subjects and in patients with congestive heart failure. Materials and MethodsThe effects of ouabain were determined in 12 normal subjects, between 18 and 49 years of age, and in 6 patients with congestive heart failure, between 34 and 52 years in age. Four of these patients had rheumatic mitral

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Section: Discussionmentioning

confidence: 83%

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Mason¹,

Braunwald²,

Karsh³

et al. 1964

J. Clin. Invest.

304

View full text Add to dashboard Cite

show abstract

“…14]. In this case, all CTSs, which are also vasotonic (198,283), would be expected to have a similar hypertensinogenic effect. When Hamlyn and his post-doc, Paolo Manunta, infused digoxin and related compounds into rats for 5 weeks, however, the BP did not rise (193,196), even though these compounds, too, are vasotonic (267,283).…”

Section: The Proof Of the Pudding Is In The Tastingmentioning

confidence: 99%

The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-Na⁺ pump endocrine system

Blaustein

2018

American Journal of Physiology-Cell Physiology

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Two prescient 1953 publications set the stage for the elucidation of a novel endocrine system: Schatzmann's report that cardiotonic steroids (CTSs) are all Na pump inhibitors, and Szent-Gyorgi's suggestion that there is an endogenous "missing screw" in heart failure that CTSs like digoxin may replace. In 1977 I postulated that an endogenous Na pump inhibitor acts as a natriuretic hormone and simultaneously elevates blood pressure (BP) in salt-dependent hypertension. This hypothesis was based on the idea that excess renal salt retention promoted the secretion of a CTS-like hormone that inhibits renal Na pumps and salt reabsorption. The hormone also inhibits arterial Na pumps, elevates myocyte Na and promotes Na/Ca exchanger-mediated Ca gain. This enhances vasoconstriction and arterial tone-the hallmark of hypertension. Here I describe how those ideas led to the discovery that the CTS-like hormone is endogenous ouabain (EO), a key factor in the pathogenesis of hypertension and heart failure. Seminal observations that underlie the still-emerging picture of the EO-Na pump endocrine system in the physiology and pathophysiology of multiple organ systems are summarized. Milestones include: 1) cloning the Na pump isoforms and physiological studies of mutated pumps in mice; 2) discovery that Na pumps are also EO-triggered signaling molecules; 3) demonstration that ouabain, but not digoxin, is hypertensinogenic; 4) elucidation of EO's roles in kidney development and cardiovascular and renal physiology and pathophysiology; 5) discovery of "brain ouabain", a component of a novel hypothalamic neuromodulatory pathway; and 6) finding that EO and its brain receptors modulate behavior and learning.

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The effect of lanatoside C on coronary vascular resistance

Gracey

Brandfonbrener

1963

American Heart Journal

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A COMPARISON OF THE DIRECT PERIPHERAL ACTIONS UPON SYSTEMIC VENOUS PRESSURE OF k‐STROPHANTHOSID, DIGOXIN AND OUABAIN

Cited by 4 publications

References 8 publications

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-Na⁺ pump endocrine system

The effect of lanatoside C on coronary vascular resistance

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A COMPARISON OF THE DIRECT PERIPHERAL ACTIONS UPON SYSTEMIC VENOUS PRESSURE OF k‐STROPHANTHOSID, DIGOXIN AND OUABAIN

Cited by 4 publications

References 8 publications

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-Na+ pump endocrine system

The effect of lanatoside C on coronary vascular resistance

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Product

Resources

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The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-Na⁺ pump endocrine system