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)

Of 165 consecutive patients undergoing computerized tomography- or magnetic resonance imaging-guided stereotactic brain biopsies at the Cleveland Clinic between June, 1987, and November, 1989, four patients (2.4%) developed arterial hemorrhage refractory to conventional efforts to secure hemostasis. Craniotomy was performed in one of these patients to control the hemorrhage; in the other three, 0.5 to 2 cc of thrombin (5000 U/cc) was slowly injected via the biopsy cannula, resulting in immediate control of bleeding in all three cases. Postoperatively, the first two patients treated with 1 to 2 cc of thrombin were slow to awaken; one had evidence of vasospasm by transcranial Doppler ultrasound studies and multiple infarcts on cranial computerized tomography, while the other had a moderate-sized frontal hematoma with intracranial hypertension. After prolonged recovery periods, only mild neurological deficits persisted in both patients. The third patient, treated with 0.5 cc of thrombin, had an uneventful postoperative course. Thrombin is highly effective for stopping intractable arterial hemorrhage during stereotactic brain biopsy; however, it is a vasospastic agent and may have been responsible for the cerebral infarctions in one patient. Therefore, thrombin should be used only as a last resort, short of craniotomy, to control intractable arterial hemorrhage during stereotactic brain biopsy.
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PMID:Treatment of intractable arterial hemorrhage during stereotactic brain biopsy with thrombin. Report of three patients. 198 4

The presence of disseminated intravascular coagulation (DIC) in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP) is debated. We assessed the occurrence of decompensated and compensated DIC (using predefined criteria) in 15 consecutive nulliparous pregnant patients with gestational hypertension combined with the HELLP syndrome and in 12 consecutive nulliparous controls with pregnancy induced hypertension (PIH) but without the HELLP syndrome. A combination of routine coagulation assays revealed the absence of decompensated DIC in all studied patients. However, using more specific and sensitive coagulation assays, compensated DIC was observed in all HELLP patients and in three patients in the control group. The mean values of antithrombin III, thrombin-antithrombin III complexes and protein C in the HELLP and the control group were 66 vs 87% (P = 0.0004), 21 vs 8 ng/ml (P = 0.0008) and 57 vs 90% (P = 0.0018) respectively. We conclude that HELLP patients show evidence of compensated DIC which may have pathophysiological significance for the observed organ damage.
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PMID:Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets. 199 31

Using fura-2 cytosolic free calcium concentrations were measured in intact washed platelets from 9 spontaneously hypertensive rats (SHR) and from 9 age-matched normotensive Wistar-Kyoto rats (WKY). In resting platelets cytosolic free calcium concentration was significantly higher in SHR than in WKY (171.8 +/- 64.4 nM vs 93.1 +/- 59.0 nM, p less than 0.05). After preincubation with erythropoietin cytosolic free calcium concentration was significantly higher in SHR than in WKY (197.5 +/- 83.2 vs 93.0 +/- 60.1, p less than 0.01). Using platelets from SHR erythropoietin increased mean resting cytosolic free calcium concentration by 14.9% (p less than 0.05) and mean thrombin induced changes of cytosolic free calcium by 58.3% (p less than 0.01). In contrast, erythropoietin caused no significant increase in the resting calcium concentration or in thrombin induced changes of cytosolic free calcium in platelets from WKY. It is concluded that erythropoietin is involved in the pathogenesis of hypertension by elevating cytosolic free calcium concentration.
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PMID:Erythropoietin increases cytosolic free calcium concentration and thrombin induced changes in cytosolic free calcium in platelets from spontaneously hypertensive rats. 205 26

The present study was designed to determine whether endothelin and "big endothelin" are released from aortic strips with endothelium and to examine the effect of thrombin by using a specific radioimmunoassay. Porcine aortic strips with endothelium released immunoreactive endothelin (ir-endothelin) and immunoreactive big endothelin (ir-big endothelin) into the medium in a time-dependent manner. These releases were markedly inhibited by 10 micrograms/ml cycloheximide. Expectedly, after removal of endothelium, aortic strips did not release a detectable amount of ir-endothelin and ir-big endothelin. In contrast, thrombin (10 units/ml) significantly stimulated the release of ir-endothelin and ir-big endothelin. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay revealed that the major component of ir-endothelin corresponds to standard endothelin-1 (1-21) and the major component of ir-big endothelin corresponds to standard big endothelin (porcine, 1-39). These results suggest that aortic strips with endothelium release endothelin and big endothelin slowly but continuously into the extracellular space and that these releases can be stimulated by thrombin.
Hypertension 1990 Jun
PMID:Release of immunoreactive endothelin from porcine aortic strips. 219 Sep 22

In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with 32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05-0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Apr
PMID:Platelet phospholipase C activity in salt-dependent hypertension. 231 20

It was reported that in essential hypertension, basal platelet free cytosolic (Ca)i measured with the fluorescent dye Quin 2, is elevated, but increases normally after thrombin stimulation. These data, were interpreted to suggest that plasma membrane fluxes are altered but the release of internal Ca2+ stores is intact. Previous studies have shown that Quin 2 inhibits Ca2+ release from internal stores following thrombin (T)-stimulation. Thus, we reassessed resting and T-stimulated platelet (Ca)i using the fluorescent dyes Fura 2 or Quin 2 in 11 subjects, 5 controls and 6 hypertensives. Mean basal (Ca)i with Quin 2 in controls was 138 +/- 15 nM vs 114 +/- 11 nM in hypertensives, (NS). By contrast, in the same platelet preparation (Ca)i with Fura 2 was higher in hypertensives than controls, 217 +/- 27 nM vs 120 +/- 4 nM, P less than .05. Blood pressure was correlated to (Ca)i obtained with Fura 2, R = 0.55. Thrombin 0.5 U/ml added to platelets in Ca-free media caused a multiphasic rise in (Ca)i with Fura 2. Although the absolute rise in (Ca)i in controls (592 +/- 104 nm) vs hypertensives (512 +/- 60 nm) did not differ, the % rise was less in hypertensives. Thus, 1) in the same population a higher resting (Ca)i was detected in platelets from essential hypertensives with Fura 2, but not with Quin 2; and 2) Ca2+ release from internal stores is altered in hypertension. Thus, Fura 2 is superior to Quin 2 in evaluating platelet (Ca)i.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Basal and stimulated cytosolic platelet calcium in essential hypertension. 233 78

There is controversy as to whether platelet intracellular free calcium ([Ca2+]i) is increased in spontaneously hypertensive rats (SHR) as compared with Wistar-Kyoto (WKY) rats. Discrepant results may be due to methodological problems including platelet activation during the collection process and leakage of intracellular dye used for [Ca2+]i measurement. To provide further insight into this problem, [Ca2+]i was estimated in fura-2-loaded platelets isolated from eight SHR and seven WKY rats at 12-14 weeks of age by using a two-syringe blood collection method and a correction method for fura-2 leakage. Basal [Ca2+]i was higher in SHR than in WKY rats (61.6 +/- 5.6 vs. 54.0 +/- 3.9 nM, p less than 0.02). However, the difference disappeared when a correction for fura-2 leakage was not used (109.7 +/- 18.4 vs. 94.9 +/- 9.2 nM, p less than 0.1). Thus, differences in [Ca2+]i between SHR and WKY rats may be obscured if dye leakage from platelets is not taken into account. Thrombin (0.1 units/ml) induced a rise in [Ca2+]i that was greater in SHR than WKY rats, both in the presence (491.4 +/- 31.6 vs. 377.5 +/- 21.7 nM, p less than 0.002) and absence (264.9 +/- 33.6 vs. 228.2 +/- 30.1 nM, p less than 0.05) of calcium in the media. These results indicate that thrombin-stimulated calcium influx as well as discharge of calcium from intracellular stores is increased in SHR platelets. Thus, under both basal and stimulated conditions, platelet calcium handling is abnormal in the SHR.
Hypertension 1990 Jun
PMID:Abnormal calcium handling by platelets of spontaneously hypertensive rats. 234 23

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18

This study examines the incidence and significance of novel plasma derived platelet aggregating activity (PAA) in 190 consecutive patients admitted to the medical wards of a general hospital. Seventy five patients (39%) demonstrated this activity. The incidence was highest in patients with a history of thrombosis (52%) or in those with a heightened thrombotic tendency, for example, patients with diabetes or hypertension. In contrast, platelet aggregating activity was observed in six out of 62 patients (approximately 10%) in whom a current or past medical history of thrombosis could not be elicited and in only two out of 72 healthy volunteers examined (3%). A high frequency of PAA was also noted in a small group of patients with idiopathic thrombocytopenia and patients who had previously received platelet transfusions. In these patients, this activity presumably reflects the presence of antiplatelet antibodies. A good correlation between the presence of plasma derived platelet aggregating activity and the phenomenon of spontaneous platelet aggregation was observed. The platelet aggregating activity was not heparin dependent, but was completely abolished by EDTA (5 mM) and benzamidine (8 mM), or by pretreating the platelets with aspirin. A synergistic response was observed with subaggregatory concentrations of thrombin and adrenalin. Our results suggest that the presence of this platelet aggregating activity may provide a marker for vascular thrombosis. Furthermore we postulate that this plasma derived activity may be partly responsible for platelet hyperactivity previously observed in patients with thromboembolic disorders.
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PMID:Platelet aggregating activity in the plasma of patients with established thrombosis. 250 37

The mechanism of platelet dysfunctions in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated. Platelet aggregation was inversely correlated with blood pressure or heart weight/body weight ratios in various strains of spontaneously hypertensive rats (SHR), indicating genetic defects. Thrombin-induced 47 kDa protein phosphorylation was markedly reduced in platelets of SHRSP compared with that in Wistar-Kyoto (WKY) rat platelets, accompanying reduced aggregation and secretion, but in 20 kDa protein phosphorylation was unchanged. Ca2+ ionophore A23187-induced responses were also significantly decreased in SHRSP, and the degrees of the changes were greater than those by thrombin. However, 12-O-tetradecanoylphorbol 13-acetate-induced responses in SHRSP were similar to those in WKY rats, suggesting that protein kinase C activity and its substrate were normally present in SHRSP platelets. Phosphatidylinositol content in platelets of SHRSP was 20% less than that in WKY rat platelets, but the contents of other phospholipids, including phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-bisphosphates, were unaltered. Thrombin-induced formation of diacylglycerols and phosphatidic acid did not differ from each other at the low concentrations. In the absence of Ca2+, thrombin-induced responses occurred to a similar degree in both platelets, whereas the enhancements by Ca2+ were much greater in WKY rats than in SHRSP. These results suggested that defective Ca2+ functions in receptor-mediated activation of protein kinase C and postkinase-mediated events appear to be an underlying mechanism for the hypofunctions in SHRSP platelets.
Hypertension 1989 Sep
PMID:Defective protein phosphorylation associated with hypofunctions in stroke-prone spontaneously hypertensive rat platelets. 250 71


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