The cardiovascular actions of WR-149,024 (1,18-diamino-7,13-diaza-9,10-dithiaoctadecane tetrahydrochloride).
1. The general cardiovascular properties of WR-149,024 (a straight chain sulphur-containing aliphatic amine) in dogs and cats are reported.2. Intravenous administration of this compound produced an immediate hypotension and bradycardia in intact anaesthetized dogs. These effects were independent of the parasympathetic nervous system since they were also present in atropinized and bilaterally vagotomized dogs.3. Ascending aortic blood flow increased after administration of WR-149,024 despite a reduction in blood pressure, contractile force and heart rate. It appears that the initial hypotension is due to a decrease in total peripheral vascular resistance since WR-149,024 produced relatively little change in force of contraction or heart rate in the isolated, blood-perfused heart preparation.4. WR-149,024 reversed the pressor effects of adrenaline within 10 min of injection while at the same time the vasopressor response to angiotensin or the vasodepressor response to isoprenaline was not altered. alpha-Adrenoceptor blockade was still evident up to five days after dosing.5. WR-149,024 did not block phenylephrine inhibition of intestinal motility. These findings suggest that WR-149,024 initiates a relatively specific and prolonged alpha-adrenoceptor blockade.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D004285:Dogs; D004562:Electrocardiography; D004837:Epinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000588:Amines; D000804:Angiotensin II; D007545:Isoproterenol; D004837:Epinephrine