Thromboxane hypertension

When given rapidly, protamine causes hypotension due to a decrease in vascular resistance, possibly linked to the release of nitric oxide from endothelium. Flypotension can be minimised by slow administration over 10-15 minutes. Protamine does not affect myocardial contractility. In some patients, systemic hypotension occurs in conjunction with pulmonary hypertension and, in severe cases, right ventricular failure. The mechanism is activation of the complement pathways by the heparin-protamine complex leading to release of thromboxane A2, which mediates pulmonary vasoconstriction. Unlike in anaphylaxis, plasma histamine concentrations are not increased. When this syndrome develops protamine administration should be stopped, and some have recommended giving heparin in an attempt to reduce the size of the heparin-protamine complex. 

The development of selective thromboxane synthase inhibitors and TXA2 receptor antagonists has required considerable effort. The resulting compounds, eg, sulotroban, have been useful for characterizing TXA2-related effects in vitro and in vivo. They are being tested in the treatment of thromboembolism, pulmonary hypertension, and preeclampsia-eclampsia. 

III. Short-Term Treatment of Ocular Hypertension A. Thromboxane A2 Receptor Agonists... 

Fluoro prostaglandin, (IV), PGF2a analogs effective as thromboxane A2 receptor agonists were prepared by Klimko (3) and used in the treatment of glaucoma and ocular hypertension. 

Bertolino F, Valentin J-P, Maffre M Jover B, Bessac A-M, John GW. Prevention of thromboxane Aj receptCH -mediated pulmonary hypertension by a nonpeptide angiotensin II type 1 receptor antagonist. J Phannacol Exp Ther 1994 268 747-52... 

Fuse S, Kamiya T. Plasma thromboxane Bj concoitration in pulmonary hypertension associated with congenital heart disease. Circulation 1994 90 2952-5... 

Boussairi EH, Sacquet J, Sassard J, Benzoni D. Thromboxane A -prostaglandin H and renovascular hypertension in rats. Am J Physiol 1994 267 R1190-7... 

Homych A, Safar M Bariity J, Simon A, Londcm G, Levenson J. Thromboxane Bj in borderline and essential hypertensive patients, l ostaglandins Leukotrienes and Medicine 1983 10 145-55... 

Ritter JM Barrow SE, Doktor HS, Stratton PD, Edwards JS, Henry JA, Gould S. Thromboxane Aj receptor antagonism and synthase inhibition in essential hypertension. Hypertension 1993 22 197-203... 

Wallenburg HCS, RotanansN. Eidianced reactivity of the platelet thromboxane pathwi in normotensive and hypertensive pregnandes witii insuffideirt fetal growth. Am J Obstet Gynecol 1982 144 523-8... 

Fitagerald D J, Rodd W, Murr R, Mayo G, FitzGerald GA. Thromboxane Aj synthesis in pregnanry-induced hypertension. Lancd 1990 335 751-4... 

NAF nafimidone. nafagrel [inn] (DP 1904) is an imidazolylmethylnaphthalenecarboxylic acid, a THROMBOXANE SYNTHETASE INHIBITOR. It inhibits renal thromboxane B2 production and renal damage in hypertensive diabetic rats, nafamostat [inn] (nafamostat mesylate [usan] nafamostat mesilate [jan] FUT 175) is a naphthyl derivative, an ENZYME INHIBITOR active as a (serine) PROTEASE inhibitor and anticomplement agent. It acts as an ANTIFIBRINOLYTIC and PLATELET AGGREGATION INHIBITOR, and can be used for the treatment of acute pancreatitis and cerebrovascular disorders. 

The effects of NCX-4016 and aspirin on the release of thromboxane TNF-a interleukin-6 and expression and activity of tissue factor (TF) in stimulated, adherent human monocytes were recently investigated (70). These data showed that NCX-4016 inhibits thromboxane generation, cytokine release, and TF activity in human monocytes via NO-dependent mechanisms. Moreover, NCX-4016 also reduces blood pressure in hypertensive rats, not simply through the direct va-sodilatory actions of the NO released by this compound, but also through possible interference with endogenous pressor compounds (71). These properties, added to its antithrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients. 

PAF released from IgE-sensitized basophilic leukocytes (and probably other mononuclear cells, such as mast cells) in response to antigen stimulation causes aggregation of platelets and release of their granular constituents (e.g., serotonin). This action of PAF is potent and rivals that of thromboxane A2 (Chapter 18). PAF also is a potent antihypertensive agent when given intravenously to hypertensive rats. It is inactivated by deacetylation by a specific acetylhydrolase. 

Platelet-activating factor—thromboxane A2- Evidence gathered from numerous experimental approaches has suggested a role for the circulating platelet in pulmonary hypertension. Platelets have been shown to aggregate... 

Arachidonic acid metabolism Lipoj genases, Prostaglandins, Thromboxanes, Cox, Leukotrienes, IT receptors Hypertension, Inflammation... 

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