Plasma Kinins Increase after Angiotensin-Converting Enzyme Inhibition in Human Subjects

1. In patients treated with angiotensin-converting enzyme inhibitors, kinin-related effects have been postulated repeatedly, but information on changes in plasma kinin levels in these patients is sparse. Difficulties in the measurement of plasma kinins account for this, at least in part. 2. The main purpose of the present study was to investigate, in normal human subjects, the effect of the angiotensin-converting enzyme inhibitor quinapril on plasma kinins. 3. High-affinity antisera (Kd <10−11 mol/l) of C-terminal specificity were raised in rabbits for radioimmunoassay of immunoreactive kinins activating the bradykinin B2-receptor, and three different liquid-and solid-phase extraction methods for plasma kinins were evaluated. Ethanol and subsequent petroleum ether extraction of 5–40 fmol of bradykinin added to plasma yielded recoveries of 39 ± 16% (mean ± SD); normal kinin levels in human plasma were 18.6 ± 3.3 pmol/l (mean ± SEM). Solid-phase extraction on urea-equilibrated phenylsilylsilica produced recoveries of 89 ± 5% and normal values of 36.4 ± 18 pmol/l. Finally, with an assay based on ethanol extraction alone, recoveries of 100 ± 16% and normal values of 16.8 ± 5.8 pmol/l were obtained, with a detection limit of 1.5 fmol/ml of plasma. Blanks were below the detection limit. Serial dilution of plasma extracts (n = 4) provided linear kinin concentrations (r = 0.99). For two different plasma pools, coefficients of variation for within-assay precision were 16.7% and 21.7%, respectively. Between-assay coefficients of variation were 12.8% and 17.4%. 4. After an oral quinapril dose of 20 mg, we found, in nine healthy men, an increase in plasma kinin levels from 16.1 ± 1.9 pmol/1 (mean ± SEM) to 22.4 ± 2.8, 23.9 ± 23, 29.1 ± 4.7 (P < 0.05) and 203 ± 4.2 pmol/1 at 2, 4, 8 and 24 h after drug intake, respectively. 5. Thus, in normal subjects treated with angiotensin-converting enzyme inhibitor plasma levels of B2-receptor stimulating kinins increase.