Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 +/- 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 +/- 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 +/- 3 vs. 48 +/- 1 nmol/liter, P < 0.005), but there were no differences in resting pHi between both groups (7.16 +/- 0.01 vs. 7.16 +/- 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 +/- 21 vs. 206 +/- 19; P < 0.05) as was the pHi increment (EH: 0.137 +/- 0.01; NT: 0.095 +/- 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pHi were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension. 800 73

The platelet intracellular calcium concentration ([Ca2+]i) and intracellular pH (pHi) were measured by spectrofluorimetry with the dyes Fura-2 and BCECF, respectively, in 19 patients with essential hypertension (10 males), aged 48 +/- 2 years, before and after 12 weeks of antihypertensive treatment and in 19 normotensive controls (11 males), aged 46 +/- 3 years. [Ca2+]i and pHi were measured in the resting state and after stimulation in vitro with 0.1 U/ml human thrombin. In patients with essential hypertension, both resting [Ca2+]i (61 +/- 4 nmol/l) and thrombin-induced maximal increase in [Ca2]i (291 +/- 26 nmol/l) were significantly (P < 0.01) greater than in the normotensive controls (resting 49 +/- 2 nmol/l and thrombin-induced 199 +/- 21 nmol/l). With respect to pHi, no difference in resting pHi between both groups was found (7.16 +/- 0.01 vs. 7.16 +/- 0.01). However, pHi increment at 300 seconds in response to thrombin was higher in the patients with essential hypertension than in the controls (0.131 +/- 0.02 vs. 0.083 +/- 0.01 pH units, P < 0.05). The increment in pHi was blunted by the amiloride derivative EIPA, indicating that it was mediated by the Na+/H+ exchanger. After antihypertensive therapy in the essential hypertensive patients, basal [Ca2+]i was significantly reduced (52 +/- 2 nmol/l, P < 0.01) and was not statistically different to the value found in the normotensive controls. Resting pHi suffered no significant modification after treatment (7.17 +/- 0.01, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of antihypertensive treatment on intracellular calcium concentration and intracellular pH in essential hypertension. 808 32

In a randomized, double-blind, crossover study our specific aim was to examine the effects of a dietary fish oil or olive oil supplementation on blood pressure, intracellular free platelet calcium, plasma lipoproteins, and circulating vasoactive substances such as norepinephrine, epinephrine, and renin in patients with essential hypertension. Ten hypertensive patients (WHO classes I, II) were randomly assigned to receive 9 g fish oil or 9 g olive oil daily for 6 weeks after a 4-week baseline period. The 6-week treatment periods were separated by a 4-week wash-out. During treatment with fish oil diastolic blood pressure decreased from 103 +/- 1 to 98 +/- 2 mmHg (P < 0.05) but did not change significantly during olive oil intake. Systolic blood pressure was not affected by either treatment. Intracellular free platelet calcium decreased in patients receiving fish oil (from 102 +/- 8 nM to 86 +/- 6 nM, P < 0.05) but was not significantly altered by olive oil treatment. In contrast, the dose-response curve for thrombin-induced intracellular free platelet calcium was not altered by the fish oil enriched diet. Plasma triglycerides decreased by approximately 40% in the fish oil group while low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol were not altered. Renin activity, norepinephrine, and epinephrine in plasma were not influenced by fish oil supplementation. We conclude that a moderate increase in dietary fish oil reduces diastolic blood pressure, intracellular free platelet calcium, and plasma triglycerides in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different effects of eicosapentaenoic acid and olive oil on blood pressure, intracellular free platelet calcium, and plasma lipids in patients with essential hypertension. 821 60

The cardiovascular risk factors blood pressure, overweight, hyperlipidaemia and several coagulation parameters were studied in a group of 54 otherwise healthy patients with essential hypertension of moderate severity. Of the 54 hypertensive patients, 43 were treated with anti-hypertensive drugs and 11 were not. The patients included in this study who were treated with anti-hypertensive drugs were still hypertensive in spite of their treatment. Lipoprotein levels and coagulation parameters did not differ between the untreated and treated hypertensive patients. Substantial percentages of patients were found to have hypertriglyceridaemia (46%), elevated LDL-cholesterol (28%) and elevated lipoprotein(a) concentrations (43%). Coagulation factors F VIIIc, fibrin monomer and factor VII in males were significantly elevated in comparison with a healthy reference group. These data are compatible with a moderate activation of the coagulation system. Correlations were established between systolic blood pressure and serum cholesterol (r = 0.43, p = 0.003), LDL-cholesterol (r = 0.34, p = 0.02) and triglycerides (r = 0.35, p = 0.01); Quetelet-index with fibrinogen (r = 0.37, p = 0.02) and thrombin-antithrombin III (r = 0.30, p = 0.04); and triglycerides with F VIIc (r = 0.34, p = 0.03) and fibrin monomer (r = 0.29, p = 0.04) respectively. These data link hypertension and hyperlipidaemia with increased coagulation activity and may contribute to our understanding of why these two cardiovascular risk factors accelerate atherogenesis.
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PMID:Coagulation factors and lipid composition of the blood in treated and untreated hypertensive patients. 846 17

Increased platelet cytosolic free calcium concentration ([Ca2+]i) has been demonstrated in both human essential hypertension and spontaneous hypertension of the rat. The present study was designed to extend the investigation on platelet Ca2+ handling to two models of salt-dependent genetic hypertension (Sabra and Dahl rat strains). No major [Ca2+]i elevation was seen in salt hypertensive SBH Sabra or SS/Jr Dahl rats. This contrasts with the data obtained in Lyon hypertensive rats (a spontaneous form of genetic hypertension) in which basal platelet [Ca2+]i was clearly increased and correlated positively with diastolic blood pressure. In these two strains, basal platelet [Ca2+]i correlated with pulse pressure but not with diastolic pressure. The absence of a significant relationship between platelet [Ca2+]i and diastolic pressure in both Sabra and Dahl rats indicates that, at least in young rats with developing salt hypertension, platelet cytosolic calcium need not reflect calcium changes occurring in the vascular smooth muscle or resistance arterioles. In contrast to the high values seen in Lyon hypertensive rats, the [Ca2+]i rise induced by thrombin was unchanged in salt-sensitive SS/Jr Dahl rats and substantially reduced in hypertension-prone SBH rats (irrespective of salt intake). The initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels was similar in SBN and SBH as well as in SR/Jr and SS/Jr rats kept on a low-salt diet but was reduced by high salt intake in platelets of salt-resistant (SBN and SR/Jr) animals only. Since platelets of Lyon hypertensive rats are also characterized by greater initial rate of thrombin-induced Mn2+ entry, this parameter was always higher in rats with established hypertension compared to their respective normotensive controls. Our study demonstrated that alterations of platelet Ca2+ handling are different in salt-dependent than in spontaneous forms of genetic hypertension.
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PMID:Platelet calcium handling is different in rats with salt-dependent and spontaneous forms of genetic hypertension. 886 28

Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca2+]i rises induced by lyso-phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [3H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of Gs with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of G alpha i2, G alpha i3, G beta 2, and G beta 4. Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits G alpha i2, G alpha i3, G beta 1, and G beta 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.
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PMID:Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated. 888 89

To clarify the relationship between cellular Ca2+ handling and salt sensitivity, we evaluated cytosolic free Ca2+ ([Ca2+]i) in fura-2 loaded platelets isolated from 20 inpatients with essential hypertension. They were placed on a low sodium diet (50 mmol/day) for one week, followed by one week on a high sodium diet (340 mmol/day). They were classified into salt-sensitive (SS, n = 8) or salt-resistant (SR, n = 12) based on changes in the mean blood pressure. During the low salt diet, basal [Ca2+]i, thrombin-evoked maximal Ca2+ responses, irrespective of the presence of 1 mM extracellular Ca2+, and ionomycin-sensitive intracellular Ca2+ discharge capacity were similar in salt-sensitive and salt-resistant patients. Platelet basal [Ca2+]i were increased in both groups by salt loading (SS, from 22.0 +/- 1.3 to 27.2 +/- 1.9 nM, p < 0.01; SR, from 20.1 +/- 0.8 to 24.4 +/- 1.3 nM, p < 0.05). The thrombin-evoked maximal Ca2+ responses both in the presence and absence of extracellular Ca2+ were unchanged by high salt intake. The rate constant of decline in Ca2+ after the peak response to thrombin was larger in SR than that in SS during the high salt diet period (SS, 0.004 +/- 0.001 sec-1; SR, 0.043 +/- 0.014 sec-1, p < 0.05). The intracellular Ca2+ discharge capacity was increased by excessive salt intake in the salt-resistant patients but was unchanged in the salt-sensitive patients (SS, from 658.1 +/- 52.8 to 639.6 +/- 91.9 nM; SR, from 690.8 +/- 65.1 to 803.3 +/- 65.1 nM, p < 0.05). An increased intracellular Ca2+ discharge capacity may play, at least in part, a significant role in preventing the elevation of blood pressure after salt loading in salt-resistant patients with essential hypertension.
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PMID:Dietary NaCl loading increases platelet Ca2+ discharge capacity in salt resistant essential hypertension. 898 2

Prothrombin activation fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III complexes (TAT) were measured in plasma of 34 patients with newly diagnosed essential hypertension. The patients with hypertension showed an increase in both F1 + 2 and TAT concentrations. The obtained results point to the intravascular thrombin generation in very early stages of essential hypertension.
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PMID:Prothrombin activation fragment 1 + 2 and thrombin-antithrombin-III complexes in plasma of patients with essential arterial hypertension. 911 58

Angiotensin II enhances platelet aggregation through activation of the G protein-linked pathway present in platelets. Studies of several angiotensin-converting enzyme (ACE) inhibitors have demonstrated marked differences on platelets. Therefore this prospective, randomized, double-blind, crossover study compared the ex vivo effects of equivalent antihypertensive doses of captopril, enalapril, and fosinopril on platelet aggregation and thromboxane B2 (TxB2) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a baseline mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enrolled. The decline in mean arterial pressure after 4 weeks of stable dosing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapril, and fosinopril, respectively (p = NS). There was no significant change in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimulated platelet aggregation from baseline or between ACE inhibitors. Compared with baseline, fosinopril decreased TxB2 concentrations 27.5-67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB2 formation, but this effect was stimulus and time dependent. Enalapril consistently increased TxB2 concentrations, independent of stimuli or time. We conclude that different ACE inhibitors have distinct effects on platelet TxB2 formation without significant effects on platelet aggregation. Fosinopril may be a direct antagonist ofTxA2 synthase, suggesting benefit in syndromes of platelet activation or vascular occlusion.
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PMID:ACE inhibitor effects on platelet function in stages I-II hypertension. 933 5

To test the hypothesis that abnormal platelet Ca2+ handling in essential hypertension results from cellular Mg2+ deficiency, cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ metabolism were studied in mag-fura 2 and fura 2-loaded platelets from 30 essential hypertensive patients and 30 sex- and age-matched normotensive controls. Basal cytosolic free Ca2+ concentration ([Ca2+]i) and intracellular Ca2+ discharge capacity were higher in hypertensives than in normotensives (22 +/- 5 vs. 18 +/- 5 nM, P < 0.05; 743 +/- 250 vs. 624 +/- 144 nM, P < 0.05, respectively). The thrombin (0. 03-1.0 U/ml)-evoked [Ca2+]i response was also enhanced in platelets from hypertensives in both the absence and presence of extracellular Ca2+. However, basal [Mg2+]i was higher in hypertensives than in normotensives (437 +/- 110 vs. 353 +/- 85 microM, P < 0.05), whereas serum Mg2+ was similar in the two groups. These results oppose the Mg2+ deficiency hypothesis in platelets in essential hypertension.
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PMID:Abnormal platelet Ca2+ handling accompanied by increased cytosolic free Mg2+ in essential hypertension. 968 95


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