Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of an endogenous natriuretic hormone and ouabain-like factors (OLF) has been postulated for many years. This postulate was based on our original observation that a small M.W. fraction in the serum after acute expansion of the extracellular fluid volume (ECFV) not only exhibited natriuretic activity but also inhibited the Na-K-ATPase enzyme in vitro similar to ouabain. Since then, numerous studies confirmed the presence of OLFs in serum, urine, cerebrospinal fluid, and various organs including the heart and hypothalamus. Some of these OLFs are well-known endogenous compounds, such as free unsaturated fatty acids, which inhibit in vitro transmembranous sodium transport, Na-K-ATPase and 3H-ouabain binding to its membrane receptor or cross-react with digoxin antibodies. Chemically yet undefined OLFs of potentially hypothalamic origin were detected in various models of experimental and clinical hypertension and are suggested to play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs isolated from the urine of salt-loaded healthy subjects strongly enhance basal and vasopressin-stimulated release of calcium in vascular smooth muscle cells and platelets similar to the effects we had observed with endothelin. This urine fraction also exhibits natriuretic activity which increases in parallel with sodium intake. Further chromatographic separation and amino acid analysis confirmed the peptidic nature (M.W. less than 1000) of the natriuretic factor(s). However, the two biological activities, namely natriuretic and ouabain-like activities, reside in distinct and chemically different compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Endogenous natriuretic and ouabain-like factors. Their potential role in volume and blood pressure regulation]. 217 10

Obesity is known to be associated with diabetes, hypertension and hyperlipidemia in the majority of the patients. There could be inaccuracy in measuring the blood pressure in obesity, therefore a cuff of sufficient size is important in blood pressure measurement. All parameters of obesity have been found to have a correlation with hypertension and it has been suggested that change in weight would cause a change in blood pressure. A weight reduction of 12 kg results in a blood pressure fall of 21/13 mm Hg. Such changes in blood pressures have been noted in untreated hypertensives. A few studies have negated the role of change in weight to have any influence on hypertension. Obesity causes a higher cardiac output and higher blood volume leading to hypertension. There may be increased intracellular sodium and reduced sodium-potassium-ATPase activity in obesity which causes increased sodium loading in hypertension. Abnormalities related to the insulin-carbohydrate metabolism and the renin-angiotensin aldosteron system have also been demonstrated in obese patients. Weight reduction also causes reduced dietary salt intake and diminished sympathetic activity. The benefits of weight reduction appear to be directly related to the amount of weight lost.
 ...
PMID:Effect of obesity and weight reduction in hypertension. 218 Feb 41

Overall, there is agreement that the origins of hypertension have a genetic basis. The genetic factors interact with environmental factors that influence expression and intensity of the disorder. As summarized in Table 1, there is evidence from the literature to identify pathways for the development of hypertension in blacks. Organ pathology, characteristic of the clinical phenotypic hypertension, consists of increased peripheral vascular resistance and left ventricular hypertrophy, and, particularly in blacks, nephrosclerosis. In this scheme, an intermediate phenotype is a biochemical or endocrine marker of gene expression that participates in the regulation of blood pressure. Intermediate phenotypic characteristics of essential hypertension include sodium sensitivity, adrenergic activity, cation transport, and endocrine function including renin-angiotensin-aldosterone, kallikrein-kinin, and prostaglandin. Another intermediate phenotype to be included in this discussion is insulin resistance. These intermediate phenotypes of cell and subcellular function are regulated by candidate genes. Alternatively, an intermediate phenotype can be expressed in response to another intermediate phenotype. For example, sodium sensitivity could be mediated by the cation transport mechanism of Na,K-ATPase, or insulin resistance could be induced by an elevated level of adrenergic activity. Gene expression of the intermediate phenotype is also modulated by environmental factors such as dietary sodium, potassium, or calcium, and social stresses or patterns of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Jun
PMID:Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture. 219 Sep 20

Endogenous factors cross-reacting with antidigoxin antibodies have been found in several tissues and body fluids of animals and humans, using commercially available digoxin radioimmunoassay or enzyme immunoassay methods. The chemical characteristics of these endogenous factors are, at present, unknown, although it has been suggested that they could be substances with low molecular weight. Experimental studies and theoretical considerations indicate that endogenous digitalis-like factors (DDLFs), in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, EDLF can be an endogenous modulator of the membrane sodium-potassium pump and several authors have suggested that EDLF could play a role in the regulation of fluids and electrolytes, muscular tone of myocardial and also in the pathogenesis of arterial hypertension. In this review, the authors discuss the hypothesis that, in metabolic diseases such as diabetes mellitus, obesity and acromegaly, the sodium retention and volume expansion, possibly due to exaggerated sodium intake, and/or exogenously induced peripheral hyperinsulinemia and high levels of growth hormone, could trigger a sustained release of EDLF, which in turn increases the blood pressure.
 ...
PMID:Is the endogenous digitalis-like factor the link between hypertension and metabolic disorders as diabetes mellitus, obesity and acromegaly? 222 23

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt intake modified cataract formation. In the present studies, we measured lens 86Rb uptake as an index of sodium-potassium adenosine triphosphatase [(Na+,K+)-ATPase] activity in weanling DS rats before the development of cataracts or sustained hypertension. Additionally, plasma renin activity was measured to indirectly assess our hypothesis that the difference between cataract-prone DS rats and DS rats unlikely to develop cataracts might be a difference in degree of salt sensitivity. At the age of 4 weeks, 50 DS and 25 salt-resistant (DR) rats were given a high sodium diet for 2 weeks, at which time the rats were divided into three groups based on the systolic blood pressure response, that is, cataract-prone DS rats with systolic blood pressure equal to or greater than 155 mm Hg, DS rats unlikely to develop cataracts with systolic blood pressure less than or equal to 125 mm Hg, and DR rats. Lens and aqueous humor Na+ and K+, lens dry weight, and water content were not significantly different among the three groups of weanling rats. Plasma renin activity was lowest in cataract-prone DS rats and low in DS rats unlikely to develop cataracts when compared with values in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Feb
PMID:Lenticular rubidium uptake and plasma renin activity in weanling cataract-prone salt-sensitive rats. 240 57

Experiments on rabbits with pituitrin hypertension have demonstrated activation of Na+, K+-ATPase of red cell membranes. Meanwhile ATPase activity declined in vasorenal hypertension. The vasodilatory drugs (papaverine, pentamine, euphylline, nicotinic acid) administered in courses normalized both the activity of transport ATPases of cell membranes and carbohydrate metabolism of blood vessels, which was disturbed in experimental vascular pathology.
 ...
PMID:[Effect of vasodilator preparations on the ATPase activity of the erythrocyte membranes of rabbits with experimental vascular pathology]. 241 92

It is now more than 10 years since we suggested that an endogenous Na+,K+-ATPase inhibitor might participate in the genesis of certain forms of ren hypertension. Although the question is not yet fully resolved, there has been much activity in the area. We here review that activity. In 1980 we reported that supernatant of boiled plasma from dogs with one-kidney, one wrapped hypertension reduces Na+-K+ pump activity when applied to an artery from another animal. Since then, we and a number of other investigators have described Na+-K+ pump inhibitory activity in the plasma of animals and humans with hypertension, particularly the low-renin varieties. The activity results from a heat-stable small molecule, but the chemical structure of the molecule is unknown. It appears to be released from the hypothalamus in response to pulmonary vascular distension and to act on blood vessels via electrogenic depolarization. Although it may be sufficient by itself to raise pressure, it may be most effective when superimposed on vascular smooth muscle cells that are abnormally permeable to Na+. Efforts to determine the chemical structure of the agent or agents should be intensified.
 ...
PMID:Evidence for a circulating endogenous Na+-K+ pump inhibitor in low-renin hypertension. 241 5

The level of circulating Na+-K+ATPase inhibitor (% inhibition), erythrocyte ouabain-sensitive 22Na+ efflux rate constant (Kos) and erythrocyte sodium content (RBC Na) were measured in 11 undialysed patients with chronic renal failure, 16 patients on chronic hemodialysis and 16 age-matched normotensive healthy controls. In uremics, % inhibition was significantly higher than that in the controls (p less than 0.001). There were significant correlations between % inhibition and both mean blood pressure (r = 0.74, p less than 0.001) and Kos (r = -0.47, p less than 0.005) for all the groups combined. Hypertensive uremics showed significantly higher % inhibition, lower Kos and higher RBC Na compared with normotensive ones. These data suggest that the elevated level of circulating Na+-K+ ATPase inhibitor may, at least in part, account for the pathogenesis of hypertension in patients with chronic renal failure.
 ...
PMID:A circulating Na+-K+ATPase inhibitor, erythrocyte sodium transport and hypertension in patients with chronic renal failure. 242 45

The prescription of cardiac glycosides is usually controlled by immunological measurement of their plasma concentration. The observation of false positive digoxin measurements in patients free of this drug and the hypothesis that endogenous digitalis-like compounds might participate in body sodium and water homeostasis have led us to investigate the presence in plasma of compounds interacting with digoxin-antibodies under various physiological and pathological conditions in man and rats. The apparent levels of digoxin-equivalents in plasma of healthy control subjects (n = 21) and patients with essential hypertension (n = 48) or end-stage renal failure (n = 13) were 24.7 +/- 3.2, 34.4 +/- 4.4 and 98.7 +/- 17.4 pg/ml, p less than 0.05 and p less than 0.01 respectively. Positive correlations were observed between systolic and diastolic blood pressure and the apparent immunoreactivity of either whole or deproteinized plasma, in particular when only male subjects were considered. No relationship was found with the renal Na+ excretion or the plasma renin activity and the apparent immunoreactivity of the plasma. Its levels were however correlated with its ability to inhibit ouabain binding to the erythrocyte Na+ pump and to its capacity to reduce the renal Na+, K+-ATPase activity. In rats with experimental hypertension, induced by chronic excess salt intake either alone or associated with reduced renal mass, the cross reactivity with antidigoxin antibodies was also enhanced when compared to control rats (71.6 +/- 10.2 pg/ml, n = 12 and 57.3 +/- 5.0 pg/ml, n = 33 respectively compared to 43.4 +/- 3.7 pg/ml, n = 36, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Compounds of the digoxin type in essential and experimental hypertension]. 243 46

Results concerning kidney and red blood cell (RBC) function of Milan hypertensive rats (MHS), and of their age- and body weight-matched normotensive controls (MNS), are summarized. Our data suggest a biochemical and physiological link between RBC abnormalities and the renal mechanisms causing hypertension in MHS, and therefore the possibility of using the former as a tool for studying the genetic biochemical mechanisms of hypertension. In particular, the following results are discussed: a positive correlation between blood pressure and RBC Na+-K+ cotransport found in the F2 generation, obtained by crossing F1 (MHS X MNS) hybrids; bone marrow transplantation from MHS and MNS into F1 hybrids, causing a parallel change in recipient RBC characteristics; and similarities between erythrocytes and renal tubular cells in Na+ content, cell volume, and Na+ transport. Ca2+ ATPase or Ca2+ pump at Vmax are lower in MHS renal tubular cells and MHS erythrocytes than in MNS cells. Moreover, isolated kidneys of MHS and MNS, perfused in vitro with media at different Ca2+ concentrations, showed that the function of MNS kidney remained stable over a range of Ca2+ from 0.75 to 1.25 mM, while the function of MS kidney deteriorated at a Ca2+ concentration of 1.25 mM.
 ...
PMID:Renal mechanisms and calcium in the pathogenesis of a type of genetic hypertension. 243 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>