Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced platelet function and a decrease in fibrinolytic activity have been reported in patients with mild hypertension after treatment with various nonselective beta-blockers. Until now, such changes have not been reported during treatment with beta 1-selective drugs or with agents that have intrinsic sympathomimetic activity. The impact of angiotensin-converting enzyme inhibitors and diuretics on platelet function and fibrinolytic activity has not been fully elucidated. Calcium antagonists of various types, however, are known to decrease platelet release in vivo whereas their effects on platelet aggregation and fibrinolytic activity are less clear. The new dihydropyridine calcium antagonist isradipine, when tested in a group of patients with mild hypertension, resulted in a decrease in platelet aggregation, a shortened euglobulin clot-lysis time, and a dramatic increase in t-PA (tissue-plasminogen activator) activity after 14 days of treatment. These changes remained stable throughout the 1-year study period. The fact that antihypertensive therapy does not always result in the hoped-for prolongation of life, despite satisfactory blood pressure reduction, may be in part due to an unfavorable impact on various components of the blood-clotting system.
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PMID:Enhanced risk of thromboembolic disease in hypertension from platelet hyperfunction and decreased fibrinolytic activity: has antihypertensive therapy any influence? 137 29

This double-blind, randomized parallel group study investigated the effect of 6 months beta-adrenoceptor antagonist therapy with either metoprolol (beta 1-selective without intrinsic sympathomimetic activity [ISA]) or epanolol (beta 1-selective with ISA) on markers of endogenous fibrinolysis in 20 patients with chronic stable angina receiving concurrent treatment with nifedipine. Neither drug had an effect on tissue-type plasminogen activator or plasminogen activator inhibitor type 1 (PAI-1). A significant correlation between fasting insulin and PAI-1 has previously been described and was confirmed in this study. The group treated with metoprolol showed a significant rise in fasting insulin after 6 months with no change in PAI-1. This suggests that the previously described link between these two may not be causal.
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PMID:The long-term effects of metoprolol and epanolol on tissue-type plasminogen activator and plasminogen activator inhibitor 1 in patients with ischaemic heart disease. 791 37

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21-39 years, during controlled frequency breathing (0.30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0.15-0.40 Hz) band (PROP 7.4 +/- 1.0; PLA 6.9 +/- 1.4; PIN 6.8 +/- 1.0 ln MI2; P = 0.003), decreased BPV in the low-frequency band (at 0.1 Hz, Mayer waves) (PROP 0.6 +/- 0.7; PLA 1.3 +/- 1.1; PIN 1.2 +/- 1.2 ln mmHg2; P = 0.001) and enhanced BRS (PROP 14.6 +/- 9.5; PLA 8.0 +/- 6.8; PIN 8.7 +/- 6.8 ms mmHg-1; P = 0.001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6.1 +/- 0.9; PLA 6.5 +/- 1.1; PIN 6.9 +/- 0.7 ln MI2; P < 0.001) and decreased Mayer waves (PROP 1.8 +/- 0.8; PLA 2.4 +/- 1.0; PIN 2.7 +/- 0.8 ln mm Hg2; P < 0.001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0.9 +/- 1.0; PLA + 0.3 +/- 1.3, PROP + 0.3 +/- 1.0 ln MI2; P = 0.026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.
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PMID:Effect of beta blockade with and without sympathomimetic activity (ISA) on sympathovagal balance and baroreflex sensitivity. 1020 Aug 96

Overactivity of the sympathetic nervous system (SNS) has been related to increased cardiovascular morbidity. Historical reports suggest hastening of blood coagulation following intravenous administration of epinephrine. Given the important role of the hemostatic system in atherosclerosis and thrombosis, it is surprising that short-term adrenergic effects on blood coagulation, fibrinolysis and platelet activity have not been scrutinized closely. To elucidate such effects in vivo, this paper reviews human studies in which alpha- and beta-sympathomimetic agents had been infused. The literature suggests a dose-dependent stimulation of factor VIII clotting activity, von Willebrand factor antigen, tissue-type plasminogen activator, and platelets within a 15- to 40-min infusion of epinephrine. Precise mechanisms underlying hemostatic changes with sympathetic activation remain to some extent speculative. However, there is evidence from adrenoreceptor blockade studies that coagulation and fibrinolysis molecules are released into circulation by stimulation of vascular endothelial beta-adrenoreceptors (most likely beta2-receptors). Combined alpha2- and beta2-adrenoreceptor-related mechanism(s) are responsible for platelet activation. Short-term activation of the SNS effects regular hemostatic activity. While in healthy individuals the hemostatic balance between coagulation and fibrinolysis may be preserved, catecholamine surge may trigger a hypercoagulable state and enhance the odds of overt thrombosis in patients with atherosclerotic disease.
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PMID:Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. 1116 93

The ability of Lys49 and Asp49 phospholipases A(2) (PLA(2)), from Bothrops asper snake venom, to cause hyperalgesia was investigated in rats, using the paw pressure test. Intraplantar injection of both toxins (5-20 micro g/paw) caused hyperalgesia, which peaked 1h after injections. Incubation of both proteins with heparin, prior to their injection, partially reduced this response. Chemical modification of Asp49 PLA(2) with p-bromophenacyl bromide (p-BPB), which abrogates its PLA(2) activity, also abolished hyperalgesia. Intraplantar injection of a synthetic peptide corresponding to the C-terminal sequence 115-129 of Lys49 PLA(2), caused hyperalgesia of similar time course, but varying magnitude, than that induced by the native protein. In contrast, a homologous peptide derived from the Asp49 PLA(2) did not show any nociceptive effect. Hyperalgesia induced by both PLA(2)s was blocked by the histamine and serotonin receptor antagonists promethazine and methysergide, respectively, by the bradykinin B(2) receptor antagonist HOE 140 and by antibodies to tumor necrosis factor alfa (TNFalpha) and interleukin 1 (IL-1). Pretreatment with guanethidine, atenolol, prazosin and yohimbine, inhibitors of sympathomimetic amines, or with indomethacin, inhibitor of the cyclo-oxygenase pathway, reduced Lys49 PLA(2)-induced hyperalgesia without interfering with the nociceptive activity of Asp49 PLA(2). The hyperalgesic response to both myotoxins was not modified by pretreatment with celecoxib, an inhibitor of the cyclo-oxygenase type II, by zileuton, an inhibitor of the lipoxygenase pathway or by N(g)-methyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthase. These results suggest that Asp49 and Lys49 PLA(2)s are important hyperalgesic components of B. asper venom, and that Lys49 and Asp49 PLA(2)s exert their algogenic actions through different molecular mechanisms.
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PMID:Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants. 1272 71