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

Ouabainlike factor (OLF) has been extracted from the hypothalamus and adrenals of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability to 1) inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, 2) displace [3H]ouabain binding, and 3) inhibit purified dog kidney Na-K-adenosinetriphosphatase (ATPase). Rat and bovine OLF have similar characteristics. Those that are close to ouabain are 1) ligand conditions for maximal inhibitory activity, 2) high-performance liquid chromatography retention time, 3) reversibility of inhibitory activity on Na-K-ATPase, 4) reduced Na-K pump inhibitory activity by K, 5) high affinity for Na-K-ATPase, and 6) no activity on calcium ATPase. OLF does not resemble ouabain in the following characteristics: 1) the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain and 2) the capacity of OLF to inhibit renal Na-K-ATPase isoforms is greater when the enzyme is obtained from adult rather than young rats. The yield of OLF is greater from MHS than MNS. These findings represent the first direct evidence that a higher amount of OLF is present in tissues from genetically hypertensive rats than from their inbred normotensive controls, maintained under the same dietary and environmental conditions. This further supports previous observations on the role of OLF in the pathogenesis of MHS hypertension.
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PMID:Ouabainlike factor in Milan hypertensive rats. 132 60

A humoral inhibitor of the membrane calcium pump was studied in plasma from 28 normal controls, 33 patients receiving long-term hemodialysis, and 26 with chronic renal failure (CRF; creatinine clearance range was 6 to 97 ml/min). Calcium pump activity was measured as the rate of Sr2+ efflux in normal erythrocytes (RBCs) loaded with Sr2+ (a substitute of Ca2+ in the calcium pump). Plasma, and plasma ultrafiltrates from hemodialysis patients strongly inhibited calcium pump activity compared with controls without plasma (36 +/- 18 vs. 25 +/- 12, %INHIBITION/CONTROL, P < 0.05). Inhibition markedly decreased with acute hemodialysis (16 +/- 12 vs. 5 +/- 14, %INHIBITION/NORMAL PLASMA, N = 15, P < 0.001). In CRF, degree of inhibition correlated with the serum creatinine concentration (r = 0.75, P < 0.001). A kinetic study showed that plasma decreased the maximal rate of the Ca2+ pumps (Vmax) without affecting the apparent affinity for internal cations (KSr). Moreover, the plasma inhibitory factor had a low molecular weight, and was dialyzable and heat stable. In conclusion, we found evidence for an RBC membrane calcium pump inhibitor in uremic plasma, which correlates with the degree of renal insufficiency. Possibly, it may increase calcium content in RBCs and other cells and could thus be related to uremic toxicity and/or hypertension.
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PMID:A circulating inhibitor of the RBC membrane calcium pump in chronic renal failure. 133 28

The ability of the Na-Ca exchanger to modify vascular relaxation was studied in rings isolated from tail arteries of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). The arteries were contracted with norepinephrine (NE) 1 microM and after stabilization they were transferred to a Ca-free physiological salt solution still in presence of NE. The time to 50% relaxation (T-50) in these conditions was significantly greater in SHRSP (78 +/- 7 s) than in WKY (50 +/- 7 s). When the calcium pump was stopped with vanadate (VAN), the Ca uptake by the sarcoplasmic reticulum with ryanodine (RY) and the Na-Ca exchanger with a Na-free PSS, the relaxation was slowed (T-50 increased to 198 +/- 16 s in SHRSP and to 162 +/- 14 s in WKY). Releasing the Na-Ca exchanger only (i.e. still with VAN and RY but with normal Na in the bath) the T-50 for relaxation in Ca-free PSS was, in WKY, nearly as fast as in control conditions (54 +/- 8 s). However, the Na-Ca exchanger in SHRSP was not so effective, and the T-50 for relaxation was slower than in control conditions (122 +/- 10 s). We conclude that the activity of the Na-Ca exchanger is depressed in tail arteries of SHRSP. This abnormality in resistance vessels, would contribute to the enhanced vascular tone present in hypertension.
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PMID:Decreased activity of the sodium-calcium exchanger in tail artery of stroke-prone spontaneously hypertensive rats. 224 41

Calcium movement across plasma membranes occurs mainly by three routes: voltage-dependent calcium channels, adenosine 5'-triphosphate-driven calcium pump, and Na+-Ca2 exchange. The regulation of the intracellular ionized calcium is the consequence of two parallel calcium transport mechanisms: a high affinity, low capacity system responsible for extruding calcium during resting conditions (calcium pump) and a low affinity and high capacity system (Na+-Ca2 antiporter). This last system is designed to extrude calcium ions when intracellular calcium rises above certain levels and also to lead calcium ions into the cell under conditions that favor the reverse mode of operation of the exchanger. This short review provides an analysis of the most conspicuous features of the two membrane transport mechanisms determined in dialyzed squid axons with special emphasis on both the complexity of the Na+-Ca2+ exchange system and its marked asymmetry.
Hypertension 1987 Nov
PMID:The squid axon as a model for studying plasma membrane mechanisms for calcium regulation. 244 78

We compared sodium-calcium (Na-Ca) exchange in vascular smooth muscle between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Aortic rings of 11 SHR and 11 WKY rats aged 11-12 weeks were superfused with physiological saline, and isometric tension was measured. Systolic blood pressure was higher in SHR (174 +/- 12 mm Hg) than in WKY rats (132 +/- 4 mm Hg): 1) In the presence of 10 microM phentolamine, 10 microM verapamil, and 5 mM caffeine, reduction of ionized extracellular sodium concentration [( Na+]o) from normal (139.2 mM) to 1.2 mM (replaced by N-methyl-D-glucamine) caused an external Ca2+-dependent increase in tonic tension (calcium entry by Na-Ca exchange). The rate of increase was higher in SHR (35.4 +/- 3.9 mg/min) than in WKY rats (17.9 +/- 1.3 mg/min) (p less than 0.01). 2) In the presence of phentolamine, verapamil, and caffeine, relaxation from low-Na+ contraction was promoted by external calcium removal. The rate of relaxation was directly related to [Na+]o. The rates of relaxation at normal (139.2 mM) [Na+]o were higher in SHR than in WKY rats (p less than 0.05). The rates of relaxation at 1.2 mM [Na+]o (calcium extrusion by adenosine triphosphate-driven calcium pump) were not different between SHR (11.6 +/- 2.8 mg/min) and WKY rats (8.9 +/- 2.5 mg/min). The increase in the rates of relaxation from 1.2 mM to normal (139.2 mM) [Na+]o (calcium extrusion by Na-Ca exchange) was greater in SHR (34.9 +/- 6.6 mg/min) than in WKY rats (17.1 +/- 4.5 mg/min) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Jun
PMID:Increased sodium-calcium exchange in arterial smooth muscle of spontaneously hypertensive rats. 273 27

Specific atrial natriuretic factor (ANF) analogues have been found to have inhibitory activity in vitro in a calmodulin-dependent, human red blood cell membrane Ca2+-adenosine triphosphatase (ATPase) model. Studied at 10(-8) to 10(-6) M concentrations, atriopeptin I (residues 127-147 of rat prepro-ANF sequence) and atriopeptin III (residues 127-150) progressively inhibited Ca2+-ATPase activity by up to 20% (p less than 0.001). This degree of inhibition was consistent with activities of other (calmodulin-independent) enzyme inhibitors in this model. Therefore, the C-terminal Phe-Arg-Tyr sequence (residues 148-150) is unnecessary for atriopeptin action on Ca2+-ATPase. Human and rat atrial peptides with amino acids 123-150 were inactive, indicating that the 123-126 sequence (Ser-Leu-Arg-Arg) must be cleaved to activate atriopeptins in this system. Human ANF fragment 129-150 also had no effect on Ca2+-ATPase, defining the importance of residues 127-128 (Ser-Ser) proximal to the disulfide bridge (joining 129 to 145). The addition of purified calmodulin to red blood cell membranes in the presence of inhibitory ANF did not restore Ca2+-ATPase activity to normal levels, indicating that the ANF effect on this enzyme is calmodulin-independent. Atriopeptin I and atriopeptin III had no effect on red blood cell Na+, K+-ATPase activity in vitro. Thus, the structure-activity relationships of ANF analogues in this novel human cell membrane model are highly specific. Although the inhibitory action of ANF analogues on Ca2+-ATPase, a calcium pump-associated enzyme, may be unique to the red blood cell, the calcium dependence of the gluconeogenic effects of ANF in the kidney would be supported by inhibition of this ATPase.
Hypertension 1988 Oct
PMID:Analogue-specific action in vitro of atrial natriuretic factor on human red blood cell Ca2+-ATPase activity. 284 69

There is growing evidence for essential or genetic hypertension to be associated with certain membrane abnormalities. We have published previous results on biochemical studies performed on erythrocyte membranes of the Okamoto-Aoki spontaneously hypertensive rat (SHR) and its normotensive control the WKY, reporting evidence of structural and functional alterations in the membranes. These changes could lead to increased calcium permeability and possibly compensatory increase in calcium pump activity that we observed concurrently. Chronic ethanol consumption resulted in mild hypertension in the rats used in the present study. The elevation in blood pressure is not associated with gross membrane changes in the erythrocyte. We noticed, however, that there is a slight elevation in the high affinity Ca2+/Mg2+-ATPase activities together with a trend towards higher osmotic fragility in the red cells of the ethanol-treated rats when compared with controls. These changes could be the result of concurrent reduction in plasma and membrane cholesterol contents also observed in the ethanol-treated animals.
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PMID:Erythrocyte membrane properties of the chronic alcoholic rat. 614 Jan 54

Calcium handling by erythrocyte membranes was compared in genetically hypertensive (SHR) and normotensive (WKR) rats by direct measurement of calcium binding, passive influx, and adenosine triphosphate (ATP)-dependent extrusion. The SHR erythrocyte membranes exhibited the following abnormalities: 1) the binding capacity of the high affinity Ca2+-binding sites located on the inner side of the membrane was 0.84 +/- 0.07 nmole/mg protein compared with 1.17 +/- 0.08 nmole/mg protein in WKR, 2) ATP-dependent Ca2+ extrusion, measured as the Ca2+ influx into inside-out vesicles, was also lower than the WKR, as was the La3+ -sensitive, Ca2+ -dependent hydrolysis, indicating reduced activity of the calcium pump; 3) the passive calcium influx into ATP-depleted red blood cells was slightly accelerated. these abnormalities in Ca2+ binding and transport probably enhanced intracellular Ca2+ concentration, and were observed under both prehypertensive an hypertensive conditions, in 3-week-old and adult SHR respectively. Similar membrane defects in excitable cells may help to explain the pathogenesis of hypertension, since they may increase vascular tone and/or catecholamine release.
Hypertension
PMID:Analysis of calcium handling in erythrocyte membranes of genetically hypertensive rats. 645 63

We previously purified to homogeneity an endogenous sodium pump inhibitor from bovine hypothalamus and hypophysis that is different from digoxin or ouabain and studied the effects of this factor on the total Ca2+,Mg(2+)-ATPase activity of plasma membrane of synaptosomes. This factor inhibits the calcium pump and the total Mg(2+)-ATPase activity of these membranes with approximately the same K0.5 values of inhibition. The potency of this factor as an inhibitor depends on the membrane concentration in the assay medium. The inhibition of the magnesium-dependent ATPase activities of these membranes was of a noncompetitive type with respect to the substrate Mg(2+)-ATP and did not significantly shift the calcium dependence of the Ca2+,Mg(2+)-ATPase activity. We suggest that the calcium pump of the synaptosomal plasma membrane is inhibited by this factor through disruption of the lipid annulus; this inhibition could play a role in the control of calcium homeostasis by increasing the cytosolic free calcium concentration.
Hypertension 1995 Mar
PMID:Modulation of the Ca2+ pump by the hypothalamic-hypophysary inhibitory factor. 787 61

Adaptive cardiac hypertrophy in the rat has been characterized as pathological or physiological reflecting the nature of the inciting stimulus. These two adaptations are distinguished by alterations in contractility and in the myosin ATPase composition of the affected muscle. We investigated the relative amounts of the mRNAs encoding cardiac sarcoplasmic reticular calcium ATPase (SERCA2), cardiac and skeletal troponin I (TnI), atrial natriuretic factor (ANF), and myosin light chain 1 (MLC1) in the hearts of rats that had been subjected to either conditioning by swimming (Sw), to renovascular hypertension (H) or to the combined stimulus (H-Sw) for 6 weeks. Compared to control animals, the mRNA levels for SERCA2 and cardiac TnI were slightly increased with Sw and moderately depressed with H. H-Sw animals showed a trend towards normalized mRNA levels for both genes. ANF mRNA levels were slightly elevated with Sw and markedly elevated with both H and H-Sw. MLC1 mRNA levels did not change with either or both stimuli. These data confirm that these two types of adaptive hypertrophy can be distinguished at the level of gene expression and suggest that the mechanical alterations seen in adaptive hypertrophy reflect a spectrum of pre-translational alterations which are not limited to changes in myosin heavy chain gene expression.
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PMID:Alterations in gene expression in the rat heart after chronic pathological and physiological loads. 819 70


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