Increased sensitivity to bradykinin among African Americans.
BACKGROUND
Angioedema is a potentially life-threatening side effect of angiotensin-converting enzyme (ACE) inhibitors. Although the mechanism of angioedema is not certain, bradykinin has been implicated in its pathogenesis. Compared with Caucasians, African Americans are at an increased risk of ACE inhibitor-associated angioedema, independent of ACE inhibitor dose or concurrent medications. Because urinary kallikrein levels are decreased in African Americans with hypertension, we hypothesized that endogenous bradykinin levels may be decreased in African Americans and that they therefore may be more sensitive to ACE inhibitor-induced increases in bradykinin or to exogenous bradykinin.


OBJECTIVE
To test this hypothesis, we measured the wheal response to intradermal injection of bradykinin in salt-replete hypertensive and normotensive African Americans and Caucasians.


METHODS
Two doses of bradykinin, 1 microgram and 10 micrograms, were administered on separate days in a randomized, double-blind fashion.


RESULTS
Higher bradykinin dose (analysis of variance: F = 38.33, p < 0.001), African American race (analysis of variance: F = 17.90, p < 0.001), and hypertension (analysis of variance: F = 4.37, p = 0.05) were all associated with an increased wheal response to bradykinin.


CONCLUSIONS
These data provide additional support for racial differences in the kallikrein-kinin system and also implicate abnormalities of the tissue kallikrein-kinin system in essential hypertension.
Gainer
J V
JV
Vanderbilt University Medical Center, Division of Clinical Pharmacology, Nashville, TN 37232-6602, USA.
Nadeau
J H
JH
Ryder
D
D
Brown
N J
NJ
D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000368:Aged; D000799:Angioedema / Q000139:chemically induced / Q000453:epidemiology / Q000208:ethnology; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000453:epidemiology* / Q000208:ethnology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000208:ethnology; D007428:Intradermal Tests; D008297:Male; D008875:Middle Aged
D001920:Bradykinin