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)

In a search for additional Ca2+ regulatory components in vascular smooth muscle, a novel troponin T-like protein was purified from bovine aorta smooth muscle. The isolated protein was separated into several isoforms on isoelectric focusing. The major isoelectric variants were focused in the pH region of 8.4 to 9.1. The protein had slightly different molecular masses in the Mr range of 35,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its molar ratio relative to tropomyosin in the muscle extract was estimated to be 0.9:1.0. The novel protein bound to the immobilized calmodulin and exhibited a number of common physicochemical properties with gizzard (Mr = 34,000) calmodulin-binding and F-actin-binding protein. The aorta and gizzard proteins were immunologically cross-reactive. Both proteins shared a common antigenic determinant with COOH-terminal segments of rabbit skeletal and bovine cardiac troponin T and bound to the immobilized smooth muscle tropomyosin. Both proteins interacted with rabbit skeletal troponin C in the presence and absence of Ca2+, but they did not interact with troponin I. These results suggest that the novel protein, which is designated calponin, may be a specialized component of smooth muscle thin filament involved in the regulation of contractile apparatus.
Hypertension 1988 Jun
PMID:Vascular smooth muscle calponin. A novel troponin T-like protein. 245 87

The correlation between the alterations of free intracellular calcium concentrations and the essential arterial hypertension has been largely investigated. Calmodulin, a cytoplasmic protein with low molecular weight, is one of the factors known to be able to affect the activity of calcium-dependent enzymes. The authors have investigated the effect of calcium and calmodulin on the plasmatic membrane of intact erythrocytes in a group of patients with essential arterial hypertension. To this purpose, the ionophor A23187, propranolol at low concentrations and a few calcium channel blocking drugs, alone or associated with calmodulin have been used. The results demonstrate that calmodulin, capable of blocking calcium outside the cell, can exert its effect only when propranolol is also present in the erythrocytes of normotensive but not in the hypertensive patients. The authors discuss some pathogenetic hypotheses.
 ...
PMID:Effects of calmodulin and calcium channel blockers on the Ca2+ induced outflow of K+ in intact red blood cells of patients with essential hypertension. 250 96

The present study was carried out to investigate the role of calmodulin in the adrenergic transmission of deoxycorticosterone acetate (DOCA)-salt hypertension. In perfused mesenteric vasculatures prepared from DOCA-salt hypertensive rats (seven to eight weeks after operation) and age-matched normotensive control rats, the effects of a specific calmodulin antagonist (W-7: N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) on the norepinephrine release and vascular responsiveness were examined. Endogenous norepinephrine overflow during electrical nerve stimulation was significantly greater in the mesenteric vasculatures of DOCA-salt hypertensive rats both at low (5 Hz) and high (15 Hz) frequencies than in those of the normotensive controls. Vasoconstrictor responses to electrical nerve stimulation or exogenous norepinephrine were also enhanced in the DOCA-salt hypertension compared to those in the controls. The calmodulin antagonist (W-7) inhibited the stimulation-evoked norepinephrine overflow and pressor responses in a dose-dependent manner. The suppressive magnitudes in these responses by W-7 were significantly greater in the mesenteric vasculatures of the DOCA-salt hypertension than in those of the control rats. These results demonstrate that the vascular adrenergic neurotransmission might be enhanced in the mesenteric vasculatures of the DOCA-salt hypertensive rats. Further, it is suggested that the marked reduction in stimulation-evoked norepinephrine overflow and vasoconstrictor responses by W-7 showed the greater calmodulin-dependent regulation in the vascular adrenergic activity of DOCA-salt hypertension.
 ...
PMID:Greater calmodulin-dependent regulation of neurotransmitter release and vascular responsiveness in chronic Doca-salt hypertension. 253 92

Previous studies have shown that erythrocytes from the Milan hypertensive strain of rats (MHS) differ from erythrocytes from the control normotensive strain (MNS). These differences are determined within the stem cells, are genetically associated with the development of hypertension, and are similar to those found between the tubular cells of the two strains. Moreover they seem to be dependent upon the presence of the membrane skeleton proteins. In this paper we describe our studies aimed at identifying some precise protein difference between the membrane skeletons of the two strains, which may cause the cellular differences described above. Milan hypertensive strain and MNS rats were immunized with ghost or membrane skeleton extracts prepared from the other or their own strains. Only MHS rats immunized with MNS ghost or membrane skeleton extracts produced an antibody against a 105 KD protein in about 95% of the animals. This protein has been identified with the recently described cytoskeletal protein adducin on the following bases: the protein binds calmodulin (CaM) and protein kinase C (PKc) in a Ca2+ dependent way. It also binds phosphatidylserine, is the substrate of exogenous PKc, and finally it is purified by high salt extraction of Triton-X100 insoluble erythrocyte cytoskeletons followed by affinity chromatography on CaM-sepharose. Using this antibody the isolation from a mouse spleen library, the characterization and sequencing of a partial cDNA clone coding for this protein has been carried out. In conclusion adducin may be considered a very useful tool to test the hypothesis that the cellular differences between MHS and MNS may be caused by a difference in a membrane skeleton protein.
 ...
PMID:Erythrocyte adducin differential properties in the normotensive and hypertensive rats of the Milan strain. Characterization of spleen adducin m-RNA. 270 90

A model of angiotensin II action has been developed in which the flow of information from cell surface to cell interior proceeds by two temporally distinct branches: a calmodulin branch largely responsible for initiating the response; and a C-kinase branch for sustaining it. There are at least two initial events: a prompt and sustained increase in calcium influx rate, and prompt hydrolysis of phosphatidylinositol 4,5-bisphosphate. The latter leads to the generation of water-soluble inositol 1,4,5-trisphosphate and lipid soluble diacylglycerol. The rise in inositol 1,4,5-trisphosphate concentration causes the redistribution of intracellular calcium, a transient rise in the calcium concentration in the cytosol, and the activation of calmodulin-dependent enzymes, including protein kinase(s). As a result, several cellular proteins are rapidly phosphorylated and initiate the cellular response. The rise in calcium and these initial phosphorylation events are transient, however, so that an additional mechanism is necessary to sustain the response. The rise in diacylglycerol content, along with the transient rise in cytosolic calcium, leads to a shift of the C-kinase from a calcium-insensitive to a calcium-sensitive, plasma membrane-associated form. In this location, the activity of C-kinase is regulated by the rate of calcium flux across the plasma membrane. As a result of the activity of the C-kinase, a second set of cellular proteins becomes phosphorylated, and these control the sustained phase of the response.
Hypertension 1987 Nov
PMID:Calcium in the regulation of aldosterone secretion and vascular smooth muscle contraction. 282 62

An apparent increase of calmodulin (CaM) activity was previously observed in the heart and kidney but not in the liver of spontaneously-hypertensive rats (SHR) and mice compared with their corresponding normotensive controls. As this change was due to an elevated recovery of CaM in the organs of the hypertensive animals, the present study was designed to evaluate its activity in hypertension. A CaM activator, detected in heart and kidney supernatants from hypertensive animals, was found to be responsible for this enhanced recovery. Similar results were obtained with passaged, cultured aortic smooth muscle cells from SHR, indicating that the anomaly was not a mere consequence of elevated blood pressure but rather a genetic expression of cells of hypertensive origin. The activator was heat stable, nondialyzable, and recovered in the fraction precipitated with 30-50% ammonium sulfate. Preliminary extraction studies suggest that the activator is contained in a glycolipid fraction. The stimulation of phosphodiesterase by this activator was calcium and CaM dependent. The activator appears to affect the affinity of the phosphodiesterase for CaM rather than the maximal stimulation. The activator was also present at a low concentration in the heart and kidney of normotensive animals. These findings indicate that at least some of the calcium abnormalities implicated in the pathogenesis of hypertension could be the result of interactions between CaM, calcium, and this activator.
 ...
PMID:Abnormality of calmodulin activity in hypertension. Evidence of the presence of an activator. 283 48

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

This study was designed to investigate the role of calmodulin in adrenergic transmission in hypertension. In perfused mesenteric vasculature from spontaneously hypertensive rats (SHR, 7-9 weeks of age) and age-matched Wistar Kyoto rats (WKY), the effects of a specific calmodulin antagonist (W-7) on norepinephrine overflow and vascular responsiveness to endogenous and exogenous norepinephrine were examined. The vasoconstrictor responses to electrical nerve stimulation and exogenous norepinephrine as well as norepinephrine overflow during electrical nerve stimulation were significantly enhanced in SHR compared with those in age-matched WKY. The calmodulin antagonist, W-7, reduced not only vasoconstrictor responses but also norepinephrine overflow during nerve stimulation. These inhibitory effects of W-7 were significantly greater in SHR than in WKY. The results demonstrate that norepinephrine overflow from the sympathetic nerve endings and vascular responsiveness were increased in SHR. The marked reduction in norepinephrine overflow and pressor responses by W-7 might suggest the greater calmodulin-dependent adrenergic transmission in this model of hypertension.
 ...
PMID:The role of calmodulin in neurotransmitter release and vascular responsiveness in spontaneously hypertensive rats. 290 79

Platelet free Ca2+ concentration has been found to be elevated in essential hypertension and to correlate with blood pressure level. Free cytoplasmic calcium concentration is determined by calcium influx, pooling, and efflux. The present study found a Ca2+-ATPase in platelet membranes that has a high affinity for Ca2+ (Km approximately 1 microM), is inhibited by low concentrations of orthovanadate (Ki approximately 1 microM), and can be stimulated by calmodulin (Km approximately 5 nM). The absolute increase in calmodulin-stimulated Ca2+-ATPase activity was not different between normotensive and hypertensive subjects; however, the degree of stimulation of Ca2+-ATPase activity at saturating calmodulin concentrations apparently was diminished in calmodulin-deficient membranes from subjects with established essential hypertension (40%) as compared to that in normotensive subjects of similar age (135%; p less than 0.001). Affinities for calmodulin and Ca2+ were comparable between the two groups, while the capacity for Ca2+-ATPase activity (basal and calmodulin-stimulated) was markedly greater (1.5- to 1.8-fold) in both native and calmodulin-deficient membranes from hypertensive subjects. On the other hand, the defective calcium efflux pump activity, as assessed by a decreased degree of calmodulin stimulation, may have contributed to elevated cytoplasmic calcium concentrations and the associated enhanced hormone sensitivity in platelets from essential hypertensive subjects. This may represent an adaptive negative feedback control mechanism to protect the cell against Ca2+ overload.
Hypertension 1986 Feb
PMID:Platelet membrane calmodulin-stimulated calcium-adenosine triphosphatase. Altered activity in essential hypertension. 293 96

Several operationally defined adenosine triphosphatase (ATPase) activities were determined in vitro in red blood cell lysates of normotensive or hypertensive humans: Mg2+-ATPase, Na+,K+-ATPase, and Ca2+ pump ATPase, the latter in the calmodulin-activated and basal states. Basal Ca2+ pump ATPase was defined as the Ca2+-activated ATPase resistant to 10(-4) M trifluoperazine. Subjects were part of a double-blind study in which treatment was divided into several phases: baseline (4 weeks), placebo or calcium (1 g elemental calcium/day, 8 weeks), placebo washout (4 weeks), placebo or calcium (1 g elemental calcium/day, 8 weeks). Irrespective of the phase of treatment, the basal Ca2+ pump ATPase activity in red blood cell lysates of 36 hypertensive subjects was significantly less than that in lysates from 18 normotensive subjects. Other ATPase activities did not differ significantly, although all ATPases tended to be decreased in hypertension. The data are consistent with previous reports of altered membrane Ca2+ binding and transport in hypertension, but the precise changes are not elucidated.
Hypertension 1986 Nov
PMID:Decreased calcium pump adenosine triphosphatase in red blood cells of hypertensive subjects. 294 85


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