Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antihypertensive activity of the nonpeptide angiotensin II receptor antagonist, SK&F 108566 (E)-alpha-[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5- yl]methylene]-2-thiophene propanoic acid), was examined in rats and dogs. SK&F 108566 produced dose-dependent decreases in blood pressure in renin-dependent hypertensive rats. At 10 mg/kg intraduodenally, mean arterial blood pressure fell from between 150-160 mm Hg to approximately 124 mm Hg. A sustained infusion of SK&F 108566 at 25 micrograms/min intraduodenally normalized blood pressure during 3 days of infusion and for 18 h following cessation of the infusion. Evaluation of the systemic hemodynamic effects of SK&F 108566 in chronically instrumented renin-dependent hypertensive rats demonstrated that the antihypertensive effects of SK&F 108566 were accompanied by a significant increase in cardiac output with little change in stroke volume. In dogs made acutely hypertensive by an intravenous infusion of angiotensin I, SK&F 108566 resulted in dose-dependent decreases in blood pressure. The antihypertensive activity of SK&F 108566 at 10 mg/kg p.o. was maintained for between 13-15 h, a similar duration of action as observed with enalapril (1 mg/kg, p.o.). Administration of DuP 753 (losartan) intravenously caused a small and short-lived fall in blood pressure in the angiotensin I-infused hypertensive dog. However, the active metabolite of losartan, EXP 3174, resulted in a response of longer duration. In dogs made hypertensive by placement of an ameroid constrictor on the left renal artery, SK&F 108566 (10 mg/kg, p.o.) or enalapril (1 mg/kg, p.o.) resulted in antihypertensive responses of at least 12 h duration. The data indicate that SK&F 108566 is a long-acting antihypertensive agent in the rat and dog.
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PMID:Antihypertensive activity of the non-peptide angiotensin II receptor antagonist, SK&F 108566, in rats and dogs. 163 91

Multiple factors are involved in thrombus formation and require complex and highly therapeutic strategies. Platelet activation plays a critical role in the genesis of acute coronary syndromes involving not only platelets but also endothelial cells, leucocytes and erythrocytes. Angiotensin II (Ang II) is a vasoconstrictor that could participate in the thrombotic process. Platelets also express Ang II AT1 type receptors on their surface. Losartan is a non-peptidic inhibitor of AT1 receptors. It has been demonstrated that losartan reduced platelet aggregation induced by the thromboxane A2 (TXA2) analogue U46619. This effect was not observed with the losartan metabolite EXP 3174. The effect of losartan was assessed in binding studies in which losartan competitively inhibited the binding of [3H]U46619 to platelets in a dose-dependent manner. Irbesartan also inhibits the TXA2 receptor in platelets, an effect that was not obtained with the active form of candesartan, CV11974, and with valsartan. These results suggest that the structural requirements necessary to antagonize the TXA2/PGH2 platelet receptor may be different from those involved in AT1 receptor antagonism. The in vivo relevance of the in vitro findings has been confirmed by the fact that in vivo administration of losartan decreases P-selectin expression in platelets obtained from stroke-prone spontaneously hypertensive rats.
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PMID:Angiotensin II AT(1) receptor antagonists and platelet activation. 1136 20