Attenuation of pressor responses to norepinephrine and pitressin and potentiation of pressor response to angiotensin II by captopril in human subjects.
The present study was conducted to investigate the influence of captopril on cardiochemodynamic responses in 38 normal volunteers (20- to 35-year-old men) to exogenously administered vasopressor substances. Norepinephrine (NE), 0.05, 0.1, and 0.2 micrograms/kg min-1; angiotensin II (AII), 5, 10, and 20 ng/kg min-1; and pitressin (2 mU/kg min-1) were infused for 10 minutes. Each infusion was reported twice, and the responses were reproducible. Captopril (50 mg by mouth) significantly attenuated the pressor responses to NE and pitressin, but the decrease in heart rate in response to NE and pitressin was almost the same before and after captopril treatment, suggesting that captopril potentiates reflex slowing of the heart. Captopril significantly potentiated the pressor response to AII. Attenuation of pressor response and potentiation of reflex slowing of the heart, in response to NE and pitressin, disappeared when a subdepressor dose of AII (1 ng/kg min-1) was infused in addition to captopril. Infusion of a subdepressor dose of bradykinin (BK), 0.1 microgram/kg min-1, had no influence on the pressor response to NE. In the subjects treated with indomethacin (225 mg/54 hrs), captopril still attenuated the pressor response to NE. These results suggest that captopril attenuates the pressor responses to NE and pitressin primarily by depletion of endogenous AII; decreased AII may desensitize the contraction of arterial smooth muscle and may potentiate the compensatory reflex mechanism.
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D012083:Renin / Q000097:blood; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D014667:Vasopressins; D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D012083:Renin; D001920:Bradykinin; D009638:Norepinephrine; D007213:Indomethacin