Role of the alpha agonist activity of dobutamine in mediating cardiac output: effects of prolonged isoproterenol infusion.
Hemodynamic activities of dobutamine enantiomers were studied in either control rats or those infused with isoproterenol (400 micrograms/kg/hr) for 4 days. In control animals prazosin attenuated the effects of (+/-)-dobutamine on cardiac output by approximately 50%; remaining activity was blocked by propranolol. After isoproterenol infusion (+/-)-dobutamine was less efficacious and the blocking effects of prazosin were greater than 90%. Isoproterenol infusion had no effect on (-)-dobutamine-mediated (alpha-1 adrenoceptor agonist) increases in cardiac output and these actions were blocked by prazosin. By contrast, compared to (+/-)- and (-)-dobutamine, effects of (+)-dobutamine (beta adrenoceptor agonist) on cardiac output were modest, not altered by prazosin and were blocked by propranolol; (+)-dobutamine was inactive after isoproterenol infusion. (-)-Dobutamine increased systemic vascular resistance in both control and isoproterenol infused rats, whereas (+)-dobutamine was inactive. (+/-)-Dobutamine increased systemic vascular resistance only in isoproterenol-infused rats. All increases in systemic vascular resistance were blocked by prazosin. Neither (+/-)- nor (+)-dobutamine significantly altered stroke volume. By contrast, (-)-dobutamine resulted in prazosin-sensitive increases in stroke volume in both control and isoproterenol-infused rats. In control animals, (+/-)-, (+)- and (-)-dobutamine increased heart rate in a dose-dependent manner; chronotropic effects of (-)-dobutamine were less than those of either (+/-)- or (+)-dobutamine. Chronotropic effects were not demonstrable in isoproterenol-infused animals. These data support the notion that in control rats cardiac output may be increased by either alpha or beta adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D004280:Dobutamine; D011433:Propranolol; D007545:Isoproterenol