Effects of angiotensin II on pressor responses to norepinephrine in humans.
In previous studies in the conscious rabbit and in isolated artery preparations, low doses of angiotensin II synergistically amplified the pressor effects of the sympathetic neurotransmitter, norepinephrine (NE). To determine whether these observations could be replicated in humans, 9 normal adult male volunteers (mean age: 34) each were given 3 i.v. doses of NE (25, 50 and 100 micrograms.kg-1.min-1) during consecutive 10 min infusion periods. On a second study day, the procedure was repeated during infusion of angiotensin II in a subpressor dose (1.25 ng.kg-1.min-1). The angiotensin II didn't alter the BP responses to NE, but it attenuated the heart rate (HR) decreases associated with the NE infusions by 80% (P less than 0.05), 42% (P less than 0.05) and 42% (P less than 0.1). The two study days were then repeated following 2 weeks of oral treatment with the angiotensin converting enzyme inhibitor captopril (which, despite significantly decreasing baseline BP, also tended to decrease HR). In the presence of captopril, the pressor responses to the NE challenges were reduced by 50% (P less than 0.05), 33% (P less than 0.05) and 13% (P less than 0.1) compared with the pre-captopril responses. Thus, angiotensin II in subpressor doses appears to enhance NE pressor effects by attenuating the compensatory HR responses, whereas inhibition of endogenous angiotensin II mechanisms weakens the BP-raising actions of NE. These findings in humans are consistent with earlier observations that the renin-angiotensin system can directly amplify sympathetic pressor effects in two separate ways: by modifying baroreceptor sensitivity and by enhancing the actions of norepinephrine on vascular smooth muscle.
Smith
D H
DH
Hypertension Center, Veterans Affairs Medical Center, Long Beach University of California, Irvine 90822.
Neutel
J M
JM
Weber
M A
MA
D000284:Administration, Oral; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects*
D000804:Angiotensin II; D002216:Captopril; D009638:Norepinephrine