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

Abnormal sodium (Na+) and water handling by the kidney may be the cause of hypertension in rats of the Milan hypertensive strain (MHS). In addition, the plasma cell membrane Ca-ATPase at Vmax is lower in MHS than in normotensive controls (MNS). The isolated kidney preparation was used to explore the role of extracellular free calcium (Ca2+) concentrations (1.25, 1.00 and 0.75 mmol/l) in tubular Na+ transport of pre-hypertensive MHS rats. At the Ca2+ concentration of 1.0 mmol/l, the following parameters were significantly higher (P less than 0.01) in MHS: glomerular filtration rate (GFR) and urinary volume (UV), +104.8 and +147.2%, respectively; urinary Na+ excretion (UNa+), +318.0%; tubular Na+ reabsorption (TNa+), +91.0% and oxygen consumption Q O2, +42.9%. Raising the Ca2+ concentration to 1.25 mmol/l increased UV (+167.0%) and UNa+ (+231.0%) in MHS without substantially affecting MNS. The difference between the two strains was therefore considerably larger for these parameters, but disappeared for TNa+ and Q O2. The overall kidney function of MHS was poor as compared wit renal function at Ca2+ 1.0 mmol/l. The differences between the two strains virtually disappeared at the lowest Ca2+ concentration (0.75 mmol/l); only GFR and TNa+ remained slightly greater in MHS mainly because of the poor viability of MNS kidneys in this experimental condition. It thus appears that the lower activity of Ca2+-ATPase of MHS compared with MNS plasma cell membranes influences the differences in Na+ and water handling in the two strains.
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PMID:Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain: role of calcium. 358 61

To determine platelet Ca2+ transport entities involved in increased cytosolic Ca2+ in the platelets of hypertensive individuals, we studied the relations between blood pressure and Ca2+ transporters in platelet membranes from 22 white male volunteers 32 to 68 years old. We used thapsigargin, a specific inhibitor of the internal membrane Ca(2+)-ATPase, to differentiate between plasma membrane and internal membrane Ca(2+)-ATPases. Inositol 1,4,5-trisphosphate-mediated and Ca2+ ionophore (A23187)-induced Ca2+ release was also assayed in membrane preparations using rhod-2, a fluorescent Ca2+ indicator. Levels of glycoprotein IIIa, a possible component of agonist-mediated Ca2+ influx, were measured by immunoblotting. The results show that plasma membrane Ca(2+)-ATPase is decreased as a function of diastolic blood pressure (P < .002), whereas the internal membrane Ca(2+)-ATPase is not (P < .148). Neither activity is correlated with age or systolic blood pressure. However, inositol trisphosphate-mediated Ca2+ release is negatively correlated with age (P < .024) but not blood pressure. Glycoprotein IIIa levels and A23187-induced Ca2+ release were not related to age or blood pressure, demonstrating that inhibition of the plasma membrane Ca(2+)-ATPase was not a result of differences in the proportion of plasma membrane in the preparation or differences in intravesicular Ca2+ concentration. Inhibition of the plasma membrane Ca(2+)-ATPase could directly cause elevation of cytoplasmic Ca2+ and enhancement of platelet sensitivity.
Hypertension 1994 Jan
PMID:Platelet calcium transport in hypertension. 828 29

1. The effects of a high calcium diet (2.5%) on blood pressure, electrolyte balance, plasma and tissue atrial natriuretic peptide (ANP), cytosolic free Ca2+ concentration ([Ca2+]i), and arterial smooth muscle responses were studied in one-kidney deoxycorticosterone (DOC)-NaCl hypertensive Wistar rats. 2. Calcium supplementation for 8 weeks markedly attenuated the development of DOC-NaCl hypertension and the associated cardiac hypertrophy, and prevented the DOC-NaCl-induced sodium-volume retention as judged by reduced plasma Na+, and decreased plasma and ventricular ANP concentrations in high calcium-fed DOC-NaCl rats. However, calcium supplementation did not affect the DOC-NaCl-induced rise in platelet [Ca2+]i. 3. Smooth muscle contractions of isolated mesenteric arterial rings in response to depolarization by K+ (20-30 mM) were enhanced in DOC-NaCl-treated rats, this enhancement being abolished by concurrent oral calcium loading. The Ca2+ entry blocker nifedipine (10 nM) inhibited the contractions induced by K+ (30-125 mM) more effectively in DOC-NaCl rats than in controls, while the inhibition in calcium-loaded DOC-NaCl rats was significantly greater than in controls only with 30 mM K+. 4. The contractions of mesenteric arterial rings induced by omission of K+ from the organ baths were used to evaluate cell membrane permeability to ions. In chemically denervated rings the onset of the gradual rise in contractile force in K(+)-free medium occurred earlier, and the rate of the contraction was faster in DOC-NaCl-treated rats than in controls and high calcium-fed DOC-NaCl rats. Smooth muscle relaxation induced by 0.5 mM K+ upon K(+)-free contractions was clearly slower in DOC-NaCl rats than in controls and calcium-supplemented DOC-NaCl rats. 5. The functions of arterial smooth muscle Na+, Ca2+ exchange and Ca(2+)-ATPase were evaluated by the aortic contractions elicited by low Na+ medium, and the subsequent relaxation responses induced by Ca(2+)-free solution (in the presence of 5 mM caffeine, 1 microM nifedipine and 10 microM phentolamine). The rate of aortic low Na+ contractions (evaluating Ca2+ influx via Na+, Ca2+ exchange), as well as that of subsequent relaxations was slower in DOC-NaCl-treated rats than in controls, whether the relaxation was induced in normal (144.0 mM) or low (1.2 mM) organ bath Na+ concentration (reflecting Ca2+ extrusion by both Ca(2+)-ATPase and Na+, Ca2+ exchange, and by Ca(2+)-ATPase alone, respectively). However, in calcium-supplemented DOC-NaCl rats the aortic responses did not differ from control. The difference between the relaxation rate in normal and low Na+ concentration in each aortic ring,representing the contribution of Na+, Ca2+ exchange in these relaxations, was comparable in all groups.6. In conclusion, calcium supplementation clearly attenuated the development of hypertension, cardiac hypertrophy, and sodium retention induced by the DOC-NaCI treatment. However, the associated rise in platelet [Ca2+], was not prevented, suggesting that in this form of experimental hypertension increased dietary calcium does not lower blood pressure by reducing [Ca2+]i. The results from vascular responses in vitro suggest that in arterial smooth muscle the DOC-NaCl treatment increased contractile sensitivity to depolarization, voltage-dependent Ca2+ entry and cell membrane permeability to ions, and attenuated relaxation responses and vascular Na+, K+-ATPase function. The results further suggest reduced ability of the cell membrane to transport Ca2+ (possibly via Ca2+-ATPase) in DOC-NaCl hypertension. The high calcium diet opposed these alterations. The present results thus provide evidence that the antihypertensive effect of a high calcium diet in mineralocorticoid-salt hypertension is mediated by its beneficial effects on systemic sodium balance and arterial smooth muscle function.
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PMID:Effects of high calcium diet on arterial smooth muscle function and electrolyte balance in mineralocorticoid-salt hypertensive rats. 848 34

We have observed previously that Ca2+ pump-mediated Ca2+ efflux is elevated in cultured aortic smooth muscle cells from spontaneously hypertensive rats compared to those from Wistar-Kyoto rat controls. The objective of this work was to determine if these strains differ in mRNA levels for the PMCA1 isoform of the plasma membrane Ca2+-ATPase and the SERCA2 isoform of the sarcoplasmic reticulum Ca2+-ATPase. mRNA levels were compared in cultured aortic smooth muscle cells from 10-week-old male rats. PMCA1 and SERCA2 mRNA levels were elevated in SHR compared to WKY. Angiotensin II increased the level of PMCA1 and SERCA2 mRNA in both strains. These studies provide further evidence for altered Ca2+ homeostasis in hypertension at the level of Ca2+ transporting ATPases in the spontaneously hypertensive rat model. These data are also consistent with the hypothesis that the expression of these two Ca2+ pumps may be linked.
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PMID:Elevated plasma membrane and sarcoplasmic reticulum Ca2+ pump mRNA levels in cultured aortic smooth muscle cells from spontaneously hypertensive rats. 901 80

The present study investigated whether functional, molecular, and biochemical alterations occurring in chronic heart failure can already be detected in compensated hypertensive cardiac hypertrophy. Force of contraction (isolated papillary muscle strip preparations), sarcoplasmic reticulum (SR) protein and myosin heavy chain isoform expression (Northern and Western blot analysis), myocardial fibrosis (collagen stains, hydroxyproline quantification), myocardial renin mRNA (RT-PCR), and angiotensin II levels and plasma aldosterone concentrations (radioimmunoassay) were studied in hypertrophied myocardium from transgenic rats harboring the mouse Ren-2d gene. Contraction and relaxation velocities of isolated papillary muscle strips were significantly reduced in cardiac hypertrophy. The beta-/alpha-myosin heavy chain ratio was significantly increased in the hypertrophied left ventricles, whereas SR Ca2+-ATPase (SERCA 2a) and phospholamban mRNA and protein levels were significantly decreased. The decrease in SERCA 2a was more pronounced than the decrease in phospholamban levels. There was no increased myocardial fibrosis. Left ventricular myocardial renin mRNA and angiotensin II concentrations, as well as plasma aldosterone levels, were higher in transgenic than in control rats. In hypertensive cardiac hypertrophy, myosin heavy chain isoform shift and reduction of SR protein levels are related to systolic and diastolic dysfunction, respectively. These alterations precede the development of myocardial fibrosis. Increased myocardial renin mRNA and angiotensin II concentrations suggest that an activated tissue renin-angiotensin system might contribute to these alterations. Since the alterations in compensated cardiac hypertrophy apparently precede those in chronic heart failure, they might accelerate the transition from hypertrophy to failure and could therefore be targets for pharmacological interventions.
Hypertension 1997 Sep
PMID:Contractile systolic and diastolic dysfunction in renin-induced hypertensive cardiomyopathy. 931 21

We have previously shown that insulin attenuates vasoconstriction, accelerates both vascular relaxation and [Ca2+]i recovery from pressor agonist-induced Ca2+ loads, and stimulates Ca2+-ATPase gene expression in rat and human vascular smooth muscle cells (VSMC). Moreover, these functions are impaired in VSMC from both insulin resistant and insulinopenic rats, suggesting that hypertension in insulin resistant states may result, in part, from impaired insulin-regulation of VSMC Ca2+ transport. Accordingly, we have now evaluated the effect of improving cellular insulin sensitivity with chromium picolinate (CrPic) on regulation of VSMC Ca2+ transport. Cultured VSMC from rats were grown from passage to confluence in the presence or absence of 1 micromol/L CrPic, maintained in a quiescent medium for 24 h and incubated with or without insulin (10(-8) mol/L) for the final 2 h. Cells were then harvested and RNA and protein extracted for Northern and Western blot analysis, respectively. Insulin caused a significant stimulation of plasmalemmal Ca2+-ATPase mRNA and protein (P < 0.05). A comparable stimulation of the mRNA and protein levels was caused by CrPic in the absence of insulin (P < 0.05), while the CrPic + insulin treatment caused a greater percentage stimulation of the Ca2+-ATPase mRNA level than either separate treatment (P < 0.05). Fluorometric analysis of the rate of [Ca2+]i recovery following stimulation with arginine vasopressin support these findings: insulin caused an 83% increase, CrPic caused a 35% increase and insulin + CrPic caused a 133% increase in [Ca2+]i recovery rate. These data suggest that CrPic may be an effective modality to reduce VSMC [Ca2+]i loads and thereby reduce peripheral vascular resistance in insulin resistant states.
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PMID:Chromium picolinate modulates rat vascular smooth muscle cell intracellular calcium metabolism. 944 40

Abnormal vascular smooth muscle (VSMC) proliferation is a key feature in diabetes-associated atherosclerotic disease. Since nitric oxide inhibits VSMC tone, migration, adhesion, and proliferation, we examined the effects of high glucose on IL-1beta-induced NO release from VSMCs in culture. Confluent smooth muscle cells, preincubated with either 5 mmol/L (mM) or 20 mmol/L (mM) glucose for 48 hours, were stimulated with IL-1beta. Nitrite was measured in the culture medium after 24 hours. IL-1beta-induced a 15-fold increase in NO production in normal glucose medium. Glucose (10 to 30 mmol/L (mM)) significantly reduced the response to IL-1beta. High glucose (20 mmol/L (mM)) inhibited IL-1beta-evoked NO production by approximately 50%. IL-1beta-stimulated [3H] citrulline-forming activity of the nitric oxide synthase (NOS) was also significantly lower in high-glucose-exposed cells, and this was reflected in diminished cellular levels of NOS protein. To assess the role of protein kinase C (PKC), membrane PKC activity was measured, and glucose (20 mmol/L (mM)) significantly increased it. Immunoblotting of the membranes revealed a glucose-induced increase in the PKC betaII isoform. 1,2-Dioctanoyl-glycerol, a PKC activator, mimicked the high-glucose effect on IL-1beta-induced NO release, while staurosporine, a PKC inhibitor, reversed it. The role of calcium in the glucose-mediated inhibition of cytokine-induced NO release was determined by treatment with BAPTA, an intracellular chelator of calcium. BAPTA partially reversed the inhibitory effects of glucose. Increasing intracellular calcium by A23187, an ionophore or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase, significantly decreased IL-1beta-induced NO release and NOS expression. These results indicate that glucose-induced inhibition of IL-1beta-stimulated NO release and NOS expression may be mediated by PKC activation and increased intracellular calcium.
Hypertension 1998 Jan
PMID:Calcium and protein kinase C mediate high-glucose-induced inhibition of inducible nitric oxide synthase in vascular smooth muscle cells. 945 18

In this work, we explored the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (Vmax) of the SERCA significantly correlated with FECa2+ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the Vmax of the SERCA (r=.462, P=.010) and the FECa2+ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca2+ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca2+ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca2+ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa2+ in the DT, and (2) a higher BP is associated with an increase in platelet Ca2+ load in human beings, expressed by a rise in the FECa2+ in the DT and the upregulation of SERCA activity.
Hypertension 1998 Feb
PMID:Ca2+ in the dense tubules: a model of platelet Ca2+ load. 946 Dec 27

The sarcoplasmic (or endoplasmic) reticulum Ca2+-ATPase (SERCA)-3 has been implicated in the possible dysregulation of Ca2+ homeostasis that accompanies the pathology of hypertension and diabetes. We report the molecular cloning of two alternatively spliced transcripts from the human SERCA3 gene, ATP2A3, that encode proteins that differ at their carboxy termini by 36 amino acids. SERCA3 transcripts were most abundantly expressed in lymphoid tissues, intestine, pancreas, and prostate. The two human SERCA3 proteins encoded by alternatively spliced transcripts were recognized by the monoclonal antibody PL/IM430 and demonstrated Ca2+ uptake and ATPase activity with an apparent Ca2+ affinity 0.5 pCa unit lower than that of other SERCA gene products. The subcellular distribution of SERCA3 protein was indistinguishable from that of SERCA2b, with expression in the nuclear envelope and in the endoplasmic reticulum throughout the cell. Two variant SERCA3 constructs, huS3-I and huS3-II, were isolated that encode proteins with three amino acid differences: Ala-673 (in huS3-I) substituted for Thr (in huS3-II), Ile-817 substituted for Met, and an insertion of Glu-994. huS3-I displayed a 10-fold lower capacity to transport Ca2+ than huS3-II.
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PMID:Functional characterization of alternatively spliced human SERCA3 transcripts. 984 5

"Remodeling" implies changes that result in rearrangement of normally existing structures. This review focuses only on permanent modifications in relation to clinical dysfunction in cardiac remodeling (CR) secondary to myocardial infarction (MI) and/or arterial hypertension and includes a special section on the senescent heart, since CR is mainly a disease of the elderly. From a biological point of view, CR is determined by 1 ) the general process of adaptation which allows both the myocyte and the collagen network to adapt to new working conditions; 2) ventricular fibrosis, i.e., increased collagen concentration, which is multifactorial and caused by senescence, ischemia, various hormones, and/or inflammatory processes; 3) cell death, a parameter linked to fibrosis, which is usually due to necrosis and apoptosis and occurs in nearly all models of CR. The process of adaptation is associated with various changes in genetic expression, including a general activation that causes hypertrophy, isogenic shifts which result in the appearance of a slow isomyosin, and a new Na+-K+-ATPase with a low affinity for sodium, reactivation of genes encoding for atrial natriuretic factor and the renin-angiotensin system, and a diminished concentration of sarcoplasmic reticulum Ca2+-ATPase, beta-adrenergic receptors, and the potassium channel responsible for transient outward current. From a clinical point of view, fibrosis is for the moment a major marker for cardiac failure and a crucial determinant of myocardial heterogeneity, increasing diastolic stiffness, and the propensity for reentry arrhythmias. In addition, systolic dysfunction is facilitated by slowing of the calcium transient and the downregulation of the entire adrenergic system. Modifications of intracellular calcium movements are the main determinants of the triggered activity and automaticity that cause arrhythmias and alterations in relaxation.
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PMID:Molecular mechanisms of myocardial remodeling. 992 72


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