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

Calcium and sodium synaptosomal uptake and mitochondrial and microsomal accumulation were examined in the brain of rats with inherited spontaneous hypertension, using 45Ca and 22Na labels. In the brain synaptosomes of hypertensive rats and control animals, calcium only arrives via potential-dependent Ca-channels when synaptolemma is depolarized. Basic calcium uptake by brain synaptosomes of hypertensive rats is increased as compared to that of the control animals. Partial depolarization of the synaptosomal plasma membrane in hypertension may be caused by its increased permeability by sodium. When Ca2+ concentrations are low, its mitochondrial accumulation rate is increased, and microsomal rate, on the contrary, decreased in the brain of hypertensive rats. The effect of calmodulin on the microsomal calcium accumulation rate is essentially lower in hypertensive rats as compared to the controls. The described disorders of synaptosomal Ca-transporting systems in rats with spontaneous hypertension can obviously result in changed neuromediator secretion rates in nerve endings.
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PMID:[Characteristics of calcium and sodium transport in the synaptosomes and subsynaptosomal structures of the brain of spontaneously hypertensive rats]. 715 14

Calcium transport to inside-out vesicles and calmodulin erythrocytic distribution were examined in primary hypertension, using the isotope exchange method and phosphodiesterase activity measurement. No differences in total erythrocyte calmodulin content and its cytoplasmic and membrane concentrations were detected in either hypertensive patients, or rats with spontaneous hypertension. Differences in the rates of calcium transport through EGTA-treated membranes were only detectable in the presence of exogenous calmodulin. The erythrocytes of hypertensive patients showed a four-fold reduction in the maximum calcium transport rate increment under the effect of calmodulin, as compared to normotensive subjects. These differences are attributed to a possible disruption of calmodulin interaction with Mg, Ca-ATPase.
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PMID:[Transport of calcium and distribution of calmodulin in the erythrocytes in primary arterial hypertension]. 716 27

A number of abnormalities in calcium homeostasis have been reported in patients with essential hypertension. IN turn, insulin has been shown to influence the activity of the Ca(2+)-ATPase. We have previously shown that normotensive offspring of essential hypertensive individuals have an exaggerated insulin response to a glucose overload. Therefore, the aim of the present study was to evaluate basal and calmodulin-activated Ca(2+)-ATPase in red blood cells and its relationship to the insulin response during an intravenous glucose tolerance test in 27 normotensive adolescents with a family history of essential hypertension (F+) (mean age, 13.9 +/- 0.5 years) and in 10 control subjects matched for age and body mass index with no family history of hypertension (F-). The results (mean +/- SD) were as follows (mumol Pi/[mg protein/h]10(-1)): basal Ca(2+)-ATPase, 4.5 +/- 1.2 in F+ and 5.1 +/- 1.6 in F- (P = NS); calmodulin-activated Ca(2+)-ATPase, 13.6 +/- 3.9 in F+ and 16.2 +/- 1.7 in F- (P < .04). The insulin area under the curve after the glucose load was 3413 +/- 1674 microU/mL per hour in F+ and 2752 +/- 928 in F- (P = NS). Calmodulin-activated Ca(2+)-ATPase showed a negative correlation with the insulin area under the curve (r = -.59, P < .005) and cholesterol levels (r = -.38, P < .03). Urinary calcium excretion was 1.82 +/- 0.9 mmol/d in F+ and 2.47 +/- 0.9 mmol/d in F- (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Dec
PMID:Calcium-ATPase and insulin in adolescent offspring of essential hypertensive parents. 749 70

Three isozymes of nitric oxide (NO) synthase (EC 1.14.13.39) have been identified and the cDNAs for these enzymes isolated. In humans, isozymes I (in neuronal and epithelial cells), II (in cytokine-induced cells), and III (in endothelial cells) are encoded for by three different genes located on chromosomes 12, 17, and 7, respectively. The deduced amino acid sequences of the human isozymes show less than 59% identity. Across species, amino acid sequences for each isoform are well conserved (> 90% for isoforms I and III, > 80% for isoform II). All isoforms use L-arginine and molecular oxygen as substrates and require the cofactors NADPH, 6(R)-5,6,7,8-tetrahydrobiopterin, flavin adenine dinucleotide, and flavin mononucleotide. They all bind calmodulin and contain heme. Isoform I is constitutively present in central and peripheral neuronal cells and certain epithelial cells. Its activity is regulated by Ca2+ and calmodulin. Its functions include long-term regulation of synaptic transmission in the central nervous system, central regulation of blood pressure, smooth muscle relaxation, and vasodilation via peripheral nitrergic nerves. It has also been implicated in neuronal death in cerebrovascular stroke. Expression of isoform II of NO synthase can be induced with lipopolysaccharide and cytokines in a multitude of different cells. Based on sequencing data there is no evidence for more than one inducible isozyme at this time. NO synthase II is not regulated by Ca2+; it produces large amounts of NO that has cytostatic effects on parasitic target cells by inhibiting iron-containing enzymes and causing DNA fragmentation. Induced NO synthase II is involved in the pathophysiology of autoimmune diseases and septic shock. Isoform III of NO synthase has been found mostly in endothelial cells. It is constitutively expressed, but expression can be enhanced, eg, by shear stress. Its activity is regulated by Ca2+ and calmodulin. NO from endothelial cells keeps blood vessels dilated, prevents the adhesion of platelets and white cells, and probably inhibits vascular smooth muscle proliferation.
Hypertension 1994 Jun
PMID:Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. 751 53

The purpose of this study was to observe the abnormalities of calcium transport of cultured arterial smooth muscle cells (ASMC) in both prehypertensive and hypertensive SHR and their control WKY rats. The changes in cAMP, ANG II and CaM contents in ASMC were also studied. The results indicated that the Ca2+ influx in ASMC of prehypertensive SHR was increased compared with that of the control, although the value of that in hypertensive SHR was higher significantly more than that of the prehypertensive rat, but there was no significant difference between them. On the other hand, the Ca2+ efflux in ASMC of prehypertensive SHR was decreased compared with that of WKY rats. A more seriously decreased efflux value was found in hypertensive SHR. The cAMP and CaM content were higher than those in WKY rats. In addition, ANG II content in ASMC had a direct bearing on blood pressure, showing a marked difference between prehypertensive and hypertensive SHR. The disturbance of transmembrane Ca2+ transport in ASMC of hypertensive rats appears to be related to genetic defect and the changes of cAMP contents might play a role in membrane Ca2+ transport in ASMC during the development of hypertension. Furthermore the level of arterial ANG II may be related to the elevation of blood pressure in hypertension.
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PMID:[The disturbance of Ca2+ transport and the changes of some relative factors in arterial smooth muscle cells from spontaneously hypertensive rats with different age]. 765 89

The possible complication of hypertension and epilepsy was investigated through the response in epileptic El mice. The systolic blood pressure in El mice (male, 8 weeks of age) and that in normal ddY mice (the parent strain of El mice) were compared by a tail-cuff method, using a programmed sphygmomanometer. The systolic blood pressure in El mice (120.5 +/- 5.6 mm Hg) was 28% (P < 0.01) higher than that in ddY mice (93.9 +/- 5.3 mm Hg). The higher systolic blood pressure in El mice was lowered by the acute intracerebroventricular administration of CaCl2 (10 mumol/kg, 30 min before measurement) or dopamine (30 nmol/mouse, 15 min before measurement), and was also improved by the chronic oral supplementation with 1.2% calcium (Ca2+) solution. Combining these results with those in our previous reports, where it is stated that lowering of Ca(2+)-calmodulin-dependent catecholamine synthesis increases the susceptibility to epileptic convulsions, we suggest that the increase in susceptibility to epileptic convulsion and occurrence of hypertension in El mice may be linked and that the two diseases may be associated.
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PMID:Hypertension in epileptic mice: a phenomenon related to reduction of Ca(2+)-dependent catecholamine synthesis in the brain. 766 12

Constitutively active nitric oxide synthases (NOS) are a unique class of NADPH-dependent, calcium/calmodulin-dependent enzymes that catalyze the conversion of L-arginine to nitric oxide and L-citrulline. However, little is known about the molecular similarities or differences between the two prototypical constitutive NOS enzymes, endothelial NOS (ECNOS) and brain NOS (bNOS). The aims of this study were to begin characterizing the gene structure and tissue distribution of messenger RNAs (mRNAs) for ECNOS and bNOS and to examine the immunological resemblance of the proteins by Western blotting. Full-length complementary DNAs (cDNAs) encoding bovine ECNOS and rat bNOS hybridized, under high stringency, to different-sized fragments of endonuclease-digested bovine, rat, and human genomic DNA. In addition, more than one fragment was detected with both cDNAs, suggesting that ECNOS and bNOS genes contained multiple introns. Tissue distribution of ECNOS mRNA (4.4 kb) and bNOS mRNA (9.5 kb) in the rat was detected by Northern blotting. Patterns among tissue extracts were strikingly different, with ECNOS mRNA being most abundant in aorta, heart, lung, kidney, adrenal gland, spinal cord, and urogenital tissues and bNOS mRNA most prominent in brain regions, intestine, stomach, spinal cord, adrenal gland, and aorta. Interestingly, ECNOS cDNA detected two equally abundant RNA transcripts (4.4 and 4.0 kb) in most brain regions tested, suggesting an alternative splicing of the ECNOS pre-mRNA. Western blotting, using an ECNOS monoclonal antibody, recognized ECNOS protein from native bovine endothelial cells, cultured bovine endothelial cells, and COS cells transfected with ECNOS cDNA but did not recognize purified bNOS.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Genomic analysis and expression patterns reveal distinct genes for endothelial and brain nitric oxide synthase. 768 5

To elucidate whether cytokines induce nitric oxide synthase in vascular smooth muscle cells, we studied the effects of human recombinant interleukin-1 beta on the synthesis and release of nitric oxide in cultured rat vascular smooth muscle cells by measurement of NO2-/NO3- levels. Furthermore, we performed Northern blot analysis using subcloned polymerase chain reaction products as probes for constitutive and inducible nitric oxide synthase. Interleukin-1 beta dose dependently (1 to 20 ng/mL) stimulated NO2-/NO3- production as a function of time. Northern blotting demonstrated the interleukin-1 beta-induced expression of messenger RNA for an inducible but not for the constitutive nitric oxide synthase after 3 hours. NG-Monomethyl L-arginine completely blocked the interleukin-1 beta-induced NO2-/NO3- production, the effect of which was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the interleukin-1 beta-induced NO2-/NO3- production in a dose-dependent manner (10(-9) to 10(-7) M) and the interleukin-1 beta-inducible nitric oxide synthase messenger RNA levels. Neither a calmodulin inhibitor (W-7) nor a protein kinase C inhibitor (staurosporine) showed any effects on the induction of nitric oxide synthase transcripts or production of NO2-/NO3- stimulated by interleukin-1 beta, whereas cycloheximide and actinomycin D completely inhibited the basal and stimulated NO2-/NO3- production. These data demonstrate for the first time that interleukin-1 beta induces gene expression of inducible nitric oxide synthase and its de novo protein synthesis in rat vascular smooth muscle cells, thereby leading to generation of nitric oxide via Ca2+/calmodulin-independent and protein kinase C-independent mechanisms.
Hypertension 1993 Jul
PMID:Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells. 768 32

Cyclosporine A (CsA)-induced hypertension appears to be caused in part by neurogenic vasoconstriction, but the mechanism by which CsA activates the sympathetic nervous system is unknown. In T lymphocytes, the cellular target of CsA and the macrolide immunosuppressant FK506 (as complexes with their endogenous cytoplasmic receptors, or immunophilins) is the Ca(2+)-calmodulin-dependent phosphatase calcineurin. The presence of calcineurin and its colocalization with immunophilin in the brain led us to hypothesize that the phosphatase also mediates CsA-induced sympathetic activation. We now report that sympathetic activity and arterial pressure in rats are increased not only by CsA but also by FK506, which is structurally unrelated to CsA but inhibits the same calcineurin-sensitive T-cell signaling pathway. In contrast, sympathetic activity and blood pressure are not increased by rapamycin, which forms an immunophilin complex that does not bind calcineurin. Furthermore, CsA- and FK506-induced sympathetic activation is attenuated for drug analogues possessing modest changes in molecular structure in a way that closely parallels the ability of each analogue to inhibit calcineurin-mediated T-cell signaling. These results implicate an important role for extralymphoid (ie, neuronal) calcineurin in mediating immunosuppressive drug toxicity.
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PMID:Cyclosporine- and FK506-induced sympathetic activation correlates with calcineurin-mediated inhibition of T-cell signaling. 768 70

The association between dietary calcium intake, calcium metabolism, and blood pressure form the basis of this review. Epidemiologic data consistently show an inverse relationship between dietary calcium and blood pressure. Clinical trials of calcium supplementation have not been as consistent in outcome. Approximately two-thirds of the supplementation studies have found a beneficial effect of calcium on blood pressure. The lack of consistency in outcome from the clinical trials relative to the epidemiological literature may be related to calcium intake. The epidemiological literature indicates an inverse relationship between calcium intake and blood pressure, with those individuals with the lowest calcium intake (< 700 mg/day) having the highest blood pressure. Clinical studies utilizing patients with high baseline calcium levels (> 700 mg/day) may not see an effect of calcium supplementation on blood pressure because of a ceiling effect. Supplemental calcium appears to correct a defect in calcium handling characterized by a renal calcium leak, increased circulating parathroid hormone, and increased intracellular calcium levels. In part, the deficit in cellular calcium homeostasis may be a consequence of abnormal calmodulin activity. Specifically, it appears that calmodulin activity is diminished in experimental hypertension and that increasing dietary calcium may improve calmodulin activity in the spontaneously hypertensive rat. The deficit in calmodulin activity has the potential to interfere with a number of cellular processes crucial to the regulation of cell function and maintenance of appropriate vascular tone. It is concluded that additional research should be directed toward understanding the ramifications of altered calmodulin activity in hypertension and the influence that dietary calcium can have on the activity of calmodulin.
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PMID:Dietary calcium, defective cellular Ca2+ handling, and arterial pressure control. 783 81


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