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      General pharmacological properties of the potent angiotensin converting enzyme inhibitor rentiapril.

      Arzneimittel-Forschung
      3-Mercaptopropionic Acid, analogs & derivatives, pharmacology, Angiotensin-Converting Enzyme Inhibitors, Animals, Antihypertensive Agents, Arousal, drug effects, Blood Coagulation, Brain, Capillary Permeability, Dose-Response Relationship, Drug, Female, Guinea Pigs, Hemodynamics, Male, Mice, Mice, Inbred Strains, Muscle, Smooth, Muscle, Smooth, Vascular, Rabbits, Rats, Rats, Inbred Strains, Respiration, Sulfhydryl Compounds, Thiazolidines

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          Abstract

          Pharmacological properties of (2R,4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), a potent inhibitor of angiotensin converting enzyme, were examined. SA 446 given intravenously lowered blood pressure in anesthetized rats and rabbits dose-dependently, while it had no remarkable effect in conscious rats even at a dose of 100 mg/kg orally or intravenously. SA 446 had no effect on heart rate in anesthetized rabbits up to 100 mg/kg i.v. In anesthetized dogs, SA 446 at a dose of 1 mg/kg i.v. produced decrease in blood pressure accompanied with coronary and vertebral arterial vasodilations, but gave no change in heart rate. SA 446 had no influence on respiration of anesthetized rabbits at doses up to 100 mg/kg i.v. The drug showed no effect on contractile force or beating rate of isolated guinea pig atria at concentrations up to 10(-4) mol/l, but caused vasoconstriction of isolated rabbit ear vessels at a 0.1 ml dose of 3 X 10(-2) mol/l solution or more and relaxation of isolated rat thoracic aortas at concentrations over 3 X 10(-4) mol/l. SA 446 had no influence on beta 1- or beta 2-adrenoceptors of isolated guinea pig atria and tracheas, respectively. Neither was a calcium antagonistic action observed. SA 446 did not influence the central nervous system, neuromuscular transmission, spontaneous movement or contractile response to several agonists of isolated smooth muscles, secretion of digestive glands, blood coagulation, hemolysis or blood glucose level, and it showed no muscle relaxant, antispasmodic or local anesthetic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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