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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An endogenous ouabain-like sodium pump inhibitor was demonstrated originally in serum or plasma of acutely extracellular fluid volume (ECFV) expanded animals and humans. Since then numerous studies have confirmed the presence of ouabain-like factor(s) (OLF) in blood, urine, cerebrospinal fluid, and various tissues including the heart and hypothalamus. Some of these OLFs represent well-known endogenous compounds, eg, free unsaturated fatty acids, which in vitro exhibit inhibition of transepithelial sodium transport, direct inhibition of the Na-K-ATPase enzyme, displacement of 3H-ouabain from its membrane receptor, and crossreaction with a digoxin antibody. Small molecular weight (MW) OLFs of yet unknown peptidic or nonpeptidic nature, which may be of hypothalamic origin, were also detected in various animal models of hypertension and in hypertensive patients. They may play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs increase basal and vasopressin-stimulated intracellular Ca2+ release in rat vascular smooth muscle cells in culture and in human platelets similar to the newly discovered endothelin. In addition, a natriuretic factor (natriuretic hormone) was detected by bioassay in plasma and urine, whose activity changes in parallel with sodium intake. We found that this natriuretic factor is associated with small peptides with a MW of less than 1,000. It is, however, unlikely that the two biological properties, ie, the ouabain-like and natriuretic activities, reside in a single compound. A number of circulating OLFs is certainly not identical with a humoral natriuretic factor. Nevertheless, there is increasing evidence for multiple interactions between OLF and the atrial natriuretic peptide (ANP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous natriuretic and ouabain-like factors. Their roles in body fluid volume and blood pressure regulation. 184 64

It has been suggested that endogenous substances (known as ouabain-like factors, OLF), secreted from the central nervous system in response to salt and water retention, inhibit the cell membrane Na+/K+ pump in the renal tubules and reduce sodium reabsorption. However, by also acting upon vascular smooth muscle cells, they may induce cell Na+ and Ca++ accumulation, vasoconstriction and systemic hypertension. Recently, an endogenous Na+/K+ pump inhibitor was isolated from human plasma; this inhibitor is indistinguishable from the cardiac glycoside ouabain based on biochemical and immunological criteria. Its plasma concentration is close to the therapeutic range for ouabain (around 0.4 nmol/L). Since plant ouabain promotes natriuresis, vasoconstriction, and hypertension; endogenous ouabain may therefore control extracellular fluid volume and blood pressure. The highest plasma concentrations of endogenous ouabain and OLF were found in congestive heart failure, aldosterone producing adenoma, human and animal models of volume expanded hypertension (reduced renal mass and DOCA-salt hypertension), and in Milan hypertensive rats (MHS). Aldosterone antagonists (canrenone and canrenoate) exert both agonist and antagonist effects on the digitalis receptor site of the Na+/K+ pump. They are effective antihypertensive agents in animal models of hypertension sustained by OLF (reduced renal mass-Na+ and DOCA-salt hypertension in rats). Moreover, in a subgroup of essential hypertensives, 4 weeks of canrenoate administration reduced blood pressure, heightened red blood cell Na+/K+ pump activity, and antagonized ouabain-induced vasoconstriction. None of these effects was seen in the other hypertensives. These data suggest that aldosterone antagonists stimulate the Na+/K+ pump inhibited by endogenous ouabain and exert their antihypertensive action at least in part through this mechanism.
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PMID:Ouabain-inhibiting activity of aldosterone antagonists. 779 94

This review examines the role of endogenous cardiac glycosides (OLF--ouabain like factors) in the pathogenesis of hypertension. The discovery of ouabain as a new adrenal hormone affecting salt and water homeostasis has initiated research on a new group of compounds. OLF may provide new insights into the mechanisms and therapy of common cardiovascular diseases. PST 2238 (17beta-(3-furyl)-5beta-androstane-3beta-14beta-17alpha-triol), an antagonist of endogenous ouabain, might open new possibilities for the therapy of hypertension and congestive heart failure.
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PMID:PST 2238 as an antihypertensive compound that antagonizes the effect of endogenous cardiac glycosides. 1602 98