caa a22 4500 469079118 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF00164582 doi (NATIONALLICENCE)springer-10.1007/BF00164582 Antihypertensive activity of the non-peptide angiotensin II receptor antagonist, SK&F 108566, in rats and dogs [Elektronische Daten] [David Brooks, Todd Fredrickson, Joseph Weinstock, Robert Ruffolo Jr., Richard Edwards, Miklos Gellai] Summary: The antihypertensive activity of the nonpeptide angiotensin II receptor antagonist, SK&F 108566 (E) - α - [[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 μg/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 1, 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. Springer-Verlag, 1992 Renin nationallicence Angiotensin II nationallicence Hypertensive dog nationallicence Hypertensive rat nationallicence SK&F 108566 nationallicence Brooks David Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut Fredrickson Todd Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut Weinstock Joseph Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut Ruffolo Jr. Robert Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut Edwards Richard Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut Gellai Miklos Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 673-678 0028-1298 345:6<673 1992 345 210 https://doi.org/10.1007/BF00164582 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00164582 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brooks David Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut NATIONALLICENCE 700 1- Fredrickson Todd Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut NATIONALLICENCE 700 1- Weinstock Joseph Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut NATIONALLICENCE 700 1- Ruffolo Jr Robert Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut NATIONALLICENCE 700 1- Edwards Richard Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut NATIONALLICENCE 700 1- Gellai Miklos Department of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, PA, USA aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 673-678 0028-1298 345:6<673 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer