Isoflavone genistein inhibits the angiotensin-converting enzyme and alters the vascular responses to angiotensin I and bradykinin.
Genistein produces antihypertensive and beneficial cardiovascular effects, although the mechanisms for these effects are not known. We examined whether genistein inhibits the in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetized rats as a result of angiotensin-converting enzyme inhibition. We have also studied the in vitro effects produced by genistein on the angiotensin-converting enzyme activity. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03 to 10 microg/kg, by angiotensin II in doses of 0.01 to 3 microg/kg, and to bradykinin in doses of 0.03 to 10 microg/kg in anaesthetized rats pretreated with vehicle (controls), or a single i.v. dose of genistein 25 mg/kg, or daily genistein 25 mg/kg i.v for two days, or a single i.v. dose of captopril 2 mg/kg. Plasma angiotensin-converting enzyme activity was determined in controls and genistein-treated rats using a fluorometric method. The effects of genistein (3-300 micromol/l) on in vitro angiotensin-converting enzyme activity were assessed by adding genistein to plasma samples and measuring angiotensin-converting enzyme activity. We found significant lower angiotensin-converting enzyme activity in plasma samples from rats pretreated with genistein compared with those found in the Control group (77.7+/-8.1 his-leu nmol/min/ml and 108.7+/-8.4 his-leu nmol/min/ml, respectively; P=0.01). The incubation of genistein with plasma samples showed that genistein decreased the angiotensin-converting enzyme activity in plasma in a concentration-dependent manner (P<0.01). These findings indicate that genistein inhibits the angiotensin-converting enzyme in vivo and in vitro and may explain, at least in part, the antihypertensive and beneficial vascular effects produced by genistein.
Montenegro
Marcelo F
MF
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
Pessa
Lisandra R
LR
Tanus-Santos
Jose E
JE
D000803:Angiotensin I / Q000008:administration & dosage*; D000804:Angiotensin II / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D019833:Genistein; D001920:Bradykinin