Chronic treatment with quercetin does not inhibit angiotensin-converting enzyme in vivo or in vitro

The precise mechanisms explaining the anti-hypertensive effects produced by quercetin are not fully known. Here, we tested the hypothesis that chronic quercetin treatment inhibits the angiotensin-converting enzyme (ACE). We examined whether quercetin treatment for 14 days reduces in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetised rats. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03-10 μg/kg, by angiotensin II in doses of 0.01-3 μg/kg, and to bradykinin in doses of 0.03-10 μg/kg in anaesthetised rats pre-treated with vehicle (controls), or daily quercetin 10 mg/kg intraperitoneally for 14 days, or a single i.v. dose of captopril 2 mg/kg. Plasma ACE activity was determined by a fluorometric method. Plasma quercetin concentrations were assessed by high performance liquid chromatography. Quercetin treatment induced no significant changes in the hypertensive responses to angiotensin I and angiotensin II, as well in the hypotensive responses to bradykinin (all p>0.05). Conversely, as expected, a single dose of captopril inhibited the hypertensive responses to angiotensin I and potentiated the bradykinin responses (all p<0.01), while no change was found in the vascular responses to angiotensin II (all p>0.05). In addition, although we found significant amounts of quercetin in plasma samples (mean=206 ng/mL), no significant differences were found in plasma ACE activity in rats treated with quercetin compared with those found in the control group (50±6 his-leu nmol/min/mL and 40±7 his-leu nmol/min/mL, respectively; p>0.05). These findings provide strong evidence indicating that quercetin does not inhibit ACE in vivo or in vitro and indicate that other mechanisms are probably involved in the antihypertensive and protective cardiovascular effects associated with quercetin.