Cardiovascular pharmacology of ASL-7022. III. Peripheral vascular adrenergic mechanisms.
The peripheral vascular actions of i.v. administered ASL-7022 were investigated in anesthetized, open-chest dogs and in isolated hindlimbs of normal, acute baroreceptor-denervated and spinal dogs. ASL-7022 decreased diastolic arterial blood pressure in open-chest dogs, an effect which was inhibited by ganglion blockade (hexamethonium bromide, 10 mg/kg i.v.). In hindlimbs from control animals, ASL-7022 produced vasodilation. Propranolol (1.0 mg/kg i.v.) reduced but did not eliminate vasodilation in these preparations but combined beta adrenergic and ganglion blockade converted responses to vasoconstriction. ASL-7022 induced greater vasodilation in hindlimbs from acute baroreceptor-denervated animals than in control animals. In acute baroreceptor-denervated preparations ganglion blockade eliminated vasodilation, propranolol partially blocked vasodilation and combined beta adrenergic and ganglion blockade converted responses to vasoconstriction. In spinal dogs i.v. infusion of low doses of ASL-7022 induced small increases in perfusion pressure; higher doses produced small decreases in perfusion pressure. The compound caused only vasoconstriction in propranolol-pretreated hindlimbs and caused only vasodilation in phentolamine-pretreated hindlimbs. ASL-7022 also dose dependently inhibited vasoconstrictor responses to electrical stimulation of the lumbar sympathetic chain and to exogenously administered norepinephrine. The data suggest that ASL-7022 blocks sympathetic vasoconstriction by either inhibiting the sympathetic nervous system or by inducing postsynaptic alpha adrenoceptor blockade. The compound also produces beta adrenoceptor-mediated vasodilation and, under appropriate pharmacological conditions, can be demonstrated to produce alpha adrenoceptor-mediated vasoconstriction.
Gorczynski
R J
RJ
Reynolds
R D
RD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000494:pharmacology*; D003714:Denervation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
D002395:Catecholamines; D006584:Hexamethonium Compounds; D018738:Hexamethonium; C036054:ASL 7022; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine