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)

Bovine albumin (BA: 2 mg/kg-1, i.v.) produced a fall in systemic arterial blood pressure accompanied by central venous hypertension and bradycardia in pentobarbital-anaesthetized, spontaneously breathing, bovine albumin-sensitized adult domestic fowl. Trasylol (a potent inhibitor of kallikreins) suppressed acute systemic anaphylaxis. Polyphloretin phosphate (an effective antagonist of PGF2alpha) also inhibited the cardiovascular responses to antigen and PGF2alpha. Sodium meclofenamate and phenylbutazone showed varying degree of blockade of cardiovascular responses to exogenously administered chemical mediators (bradykinik, PGF2alpha, SRS-A and to a lesser extent of histamine, 5-HT and acetylcholine) and antigen. Indomethacin (virtually devoid of receptor blocking activities toward exogenously injected chemical mediators) inhibited anaphylaxis. The results of this investigation strongly suggested an important role of vasoactive lipids and polypeptides in avian anaphylaxis.
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PMID:Acute systemic anaphylaxis in adult domestic fowl--possible role of vasoactive lipids and peptides. 31 23

A 29-year-old woman suffered acute laryngospasm on taking the initial dose of propranolol hydrocholoride for the treatment of hypertension associated with a hyperdynamic circulatory state. Hypersensitivity to the tartrazine additive used as a stabilizing agent in oral propranolol appeared the likely cause of anaphylaxis, although a direct hypersensitivity to propranolol itself could not be excluded.
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PMID:Allergic laryngospasm on initiating oral propranolol therapy. 90 Oct 92

R24 is a mouse IgG3 monoclonal antibody that reacts with the ganglioside GD3 expressed by melanoma cells and other cells of neuroectodermal origin (e.g. adrenal medulla). Antitumour activity of R24 was demonstrated in initial phase I and pilot trials, but treatment was limited by urticaria at cumulative doses of 400 mg/m2. A trial exploring intensification of the dose of R24 was conducted in eight patients. Planned doses of R24 antibody were 800 and 1200 mg/m2 over 6-8 days by continuous i.v. infusion. All patients received concomitant therapy with hydroxyzine hydrochloride and cimetidine to minimize urticaria. One patient developed anaphylaxis, after which no further therapy was given. All patients developed peripheral blood lymphopenia and marked decreases in serum complement values during treatment, suggesting depletion of two possible effector mechanisms of the antitumour effects of R24. A vascular leak syndrome, manifested by weight gain, oedema and hypotension, was evident in seven patients during the initial 24-36 h of treatment. Serum sickness syndrome was observed in six of seven evaluable patients between days 5 and 8, coincident with the onset of the human anti-globulin response to R24. One patient given 1200 mg/m2 had a minor response (38% reduction in pelvic nodes) lasting 12 months. There was no detectable increase (by immunohistochemical staining) in deposition of R24 within tumour sites at doses used in this trial compared to that observed at doses of 240 and 400 mg/m2. The maximum tolerated dose was 800 mg/m2. Dose-limiting toxicity was manifest as reversible hypertension with end-organ symptoms (chest pain or visual field defects) in patients treated with a dose of 1200 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment with high dose mouse monoclonal (anti-GD3) antibody R24 in patients with metastatic melanoma. 129 83

The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 micrograms of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 +/- 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA). PLA and Paorta then increased above baseline and heart rate deceased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1 alpha did not increase following LTD4 infusion. The increase in PPA after 3-micrograms injections of LTD4 was greater than that caused by 10-micrograms injections of prostaglandin H2-analog. Injections of 10-30 micrograms of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta. The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta. The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism.
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PMID:Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. 311 26

Acetyl-glyceryl-ether-phosphoryl-choline (AGEPC) is a potent platelet activating factor which induces profound circulatory changes. AGEPC is synthesized in a variety of cell types including platelets, neutrophils, macrophages, basophils and endothelial cells. Biological responses include platelet activation, neutrophil activation, release of arachidonic acid metabolites and systemic anaphylaxis. Circulatory responses to AGEPC were evaluated in the present investigation. Intravenous administration of AGEPC (30 micrograms/kg/min) to anesthetized dogs reduced blood pressure, cardiac output, myocardial contractile force, renal blood flow and glomerular filtration. Intracoronary administration of AGEPC (0.3-3 micrograms) reduced blood pressure, coronary blood flow, and myocardial contractile force. Administration of AGEPC into the femoral vascular bed increased femoral artery blood flow. The data suggest that the circulatory response to AGEPC in the dog is complex and depends on the site of administration. The predominant response is hypotension mediated at least in part through myocardial depression. Intramuscular injection of AGEPC (10-30 micrograms/kg) to conscious spontaneously hypertensive rats (SHRs) reduced systemic blood pressure and increased heart rate. In pithed rats, AGEPC decreased pressor responses to sympathetic stimulation, angiotensin II and phenylephrine. Chronotropic responses were unchanged. Thus, antihypertensive doses of AGEPC reduced pressor responsiveness nonspecifically, but do not affect pre- or post-junctional adrenergic mechanisms. High concentrations of AGEPC (100 microM) relaxed phenylephrine contracted rabbit aortic rings. Relaxation was dependent on an intact endothelium. Lyso-GEPC produced similar actions. In light of the low potency of AGEPC and the activity of lyso-GEPC, physiological significance to endothelium dependent relaxation by AGEPC in rabbit aortic rings is unlikely. The physiological role of AGEPC in circulatory homeostasis is unclear at present. AGEPC may play a hypotensive role in some forms of experimental hypertension. In addition, AGEPC may mediate part of the circulatory derangements associated with cardiac anaphylaxis. Lastly, AGEPC may be involved in circulatory control during states of platelet and/or neutrophil activation such as myocardial ischemia and shock.
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PMID:AGEPC, a vasodilator phospholipid with profound circulatory actions. 353 24

To further clarify the platelet dependence of acetyl glyceryl ether phosphorylcholine (AGEPC) physiologic activity and of IgE anaphylaxis in the rabbit, PGI2 was employed as an inhibitor of in vivo platelet function. Intravenous infusion of PGI2 (1 to 2 micrograms/kg/min) inhibited the AGEPC-induced decrease in dynamic compliance, increase in total pulmonary resistance, and transient decrease in tidal volume, but the right ventricular hypertension, bradycardia, and apnea were unaffected. Although PGI2 itself produced a marked systemic hypotension, AGEPC still induced a bimodal hypotensive response. Documentation that platelet function was inhibited by PGI2 included partial inhibition of AGEPC-induced thrombocytopenia, abrogation of platelet secretion (as assessed by plasma platelet factor 4 levels), and inhibition of ex vivo platelet aggregation. The AGEPC-induced leukopenia was not affected. In another group of rabbits, chlorpheniramine pretreatment inhibited the lung mechanical changes induced by AGEPC but did not affect the ventilatory or circulatory alterations, indicating that the lung mechanical alterations (but not any of the other alterations) are mediated by platelet-secreted histamine acting via H1 receptors. In IgE-producing rabbits intravenously challenged with antigen, PGI2 had no effect on any of the physiologic alterations, despite substantial inhibition of platelet secretion. From these results, together with previous platelet depletion studies, we conclude that AGEPC may be a significant mediator of the circulatory alterations and apnea of rabbit IgE anaphylaxis by platelet-independent mechanisms, but neither AGEPC nor platelets appear to be important in mediating the anaphylactic lung mechanical alterations.
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PMID:Participation of platelets in the physiologic alterations of the AGEPC response and of IgE anaphylaxis in the rabbit. Effects of PGI2 inhibition of platelet function. 388 Oct 60

Leukotriene D4, a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by hypotensive shock in spontaneously hypertensive rats but not in other rats. Hemodynamic mechanisms underlying this pattern in spontaneously hypertensive rats, pithed and vagotomized to eliminate circulatory reflexes, were studied using radiolabeled microspheres. One minute after leukotriene D4 administration (20 micrograms/kg i.v.), mean arterial pressure increased by 54 mm Hg, total peripheral resistance index increased by 68%, heart rate decreased by 34 beats/minute, and cardiac index was unchanged. Profound reductions of blood flow and increases of vascular resistance in the hepatosplanchnic area, skeletal muscles, and skin also occurred. Five minutes later, mean arterial pressure remained elevated (+35%), hematocrit rose (+17%), and total peripheral resistance index increased, which offset 40% decreases in cardiac and stroke volume indices. Ten minutes after leukotriene D4 administration, during hypotension, cardiac and stroke volume indices and blood flow to all vascular beds declined further while total peripheral resistance index and hematocrit (+28%) continued to rise. In Wistar-Kyoto rats, administration of leukotriene D4 caused less of a pressor response (+34 mm Hg) because vascular resistance was increased only in skeletal muscles, which was followed by a slight hypotension without any significant changes in cardiac and stroke volume indices, total or regional vascular resistance, and hematocrit. Thus, in spontaneously hypertensive rats the leukotriene D4-induced pressor response appears to be caused by generalized vasoconstriction, and the subsequent hypotension appears to result not from vascular collapse but from reduced cardiac output.
Hypertension
PMID:Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats. 400 88

1. Acute systemic anaphylaxis in calves was characterized by marked systemic hypotension; hypertension in the pulmonary arteries and abdominal vena cava, and transient apnoea. Calves responded with a second reaction to antigen, but a third anaphylactic response could not be evoked.2. Suppression of systemic anaphylaxis could not be effected with mepyramine, whereas methysergide or diethylcarbamazine each suppressed anaphylaxis by 50%. Disodium cromoglycate alone did not inhibit anaphylaxis: however, when disodium cromoglycate was combined with diethylcarbamazine almost total suppression (85%) was achieved. Sodium meclofenamate also was a powerful inhibitor of anaphylaxis (80%). It is tentatively suggested that slow reacting substance (SRS-A) may be an important mediator of bovine anaphylaxis.3. Bilateral vagotomy did not modify the circulatory responses to injected histamine, 5-hydroxytryptamine (5-HT) or antigen, whereas the effects of these agents on ventilation (apnoea) were abolished by vagotomy.4. Plasma histamine concentration was increased during anaphylaxis, whereas plasma 5-HT was not. Whole blood histamine concentration fell sharply and remained depressed during 20 min of anaphylactic shock. Reduced whole blood histamine levels probably reflect the severe leucopoenia in the calves.5. Histamine concentrations in six tissues taken from calves subjected to anaphylaxis were not different from those in control calves; mast cells were of similar numbers to controls, but showed some swelling, granular spilling and metachromasia.6. Histamine, 5-HT, bradykinin and antigen caused increased pulmonary artery perfusion pressure and ventilation resistance in isolated lungs from sensitized calves. However, there was no difference in histamine and 5-HT concentration in perfusates obtained during antigen infusion of sensitized and control lungs.7. Systemic anaphylaxis of calves may result from the interaction of histamine, 5-HT and SRS-A. The present data implicate (by indirect measurement) SRS-A as an important mediator of anaphylaxis in this species.
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PMID:Acute systemic anaphylaxis in the calf. 414 91

Anaphylaxis to known allergens occurred in two patients under treatment for hypertension with propranolol. The clinical course of both cases was similar. Bradycardia associated with an undetectable blood pressure, unusual severity, and sluggish response to treatment were major common factors in which blockade of the beta-adrenergic system may have had a role. Propranolol, a beta-adrenergic antagonist that acts competitively by blocking the adenylate cyclase receptor on efferent cells, is well recognized to cause increased airways resistance in some asthmatic and normal subjects. It is postulated that propranolol potentiated anaphylaxis in these patients by inhibition of adenylate cyclase, resulting in lowered intracellular cyclic AMP and a lowered threshold of mediator release. The bradycardia during profound hypotension is attributed to an unopposed cholinergic action caused by blunting of the normal endogenous beta-adrenergic response by propranolol.
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PMID:Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade. 611 16

Pentobarbital-anesthetized and spontaneously breathing, bovine albumin (BA)-sensitized adult domestic fowl showed acute systemic anaphylaxis to IV injection of antigen (BA), which was characterized by arterial hypotension, central venous hypertension, and bradycardia. Large doses of pyrilamine maleate (/1-receptor antagonist) partially inhibited acute systemic anaphylaxis. On the other hand, metiamide (a specific H2-antagonist) and propranolol (beta-adrenergic antagonist) markedly enhanced the anaphylactic response. Terbutaline (beta 2-agonist), dimaprit (a highly selective H2-agonist), and compound FPL 55712 (a slow-reacting substance of anaphylaxis receptor antagonist) either significantly inhibited or reversed the anaphylactic response. Cimetidine (a newer H2-antagonist) enhanced only central venous pressor response to BA. This investigation appears to suggest a minor role of histamine and a major role of slow-reacting substance of anaphylaxis as chemical mediatiors of anaphylaxis. A protective role of beta 2-adrenergic and H2-histaminergic receptors seem to operate in immediate hypersensitivity reactions in adult domestic fowl.
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PMID:Acute systemic anaphylaxis in adult domestic fowl: evidence for the protective role of H2-histaminergic and beta 2-adrenergic receptors. 624 59


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