Role of TXA2 in the pathogenesis of severe angiotensin II-salt hypertension.
Urinary TXB2 excretion and the release of TXB2 from vascular and renal cortical tissues are increased in rats with severe AII-salt hypertension. Treatment with an inhibitor of TXA2 synthesis did not change the blood pressure of normotensive or of AII-salt hypertensive rats. Treatment with SQ29,548, a TXA2 receptor antagonist, caused reduction of blood pressure and renal vascular resistance in AII-salt hypertensive but not in normotensive rats. We conclude that the SQ29,548-induced lowering of blood pressure and renal vascular resistance in AII-salt hypertensive rats is the result of blockade of the vascular actions of one or more pressor eicosanoids including TXA2 and the prostaglandin endoperoxides. A corollary of this conclusion is that pressor eicosanoids may be contributory factors in the pathogenesis of severe AII-salt hypertension in rats.
Mistry
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Department of Pharmacology, University of Tennessee, Memphis 38163.
Nasjletti
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D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007672:Kidney Cortex / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D012982:Sodium, Dietary; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013929:Thromboxane B2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007093:Imidazoles; D012982:Sodium, Dietary; D000804:Angiotensin II; C039242:dazmegrel; D013929:Thromboxane B2; D013928:Thromboxane A2; C045749:SQ 29548; D013930:Thromboxane-A Synthase