ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries. Biol Chem 2013 Sep;394(9):1205-12
Date
06/05/2013Pubmed ID
23729620Pubmed Central ID
PMC3979287DOI
10.1515/hsz-2012-0348Scopus ID
2-s2.0-84881500282 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Bradykinin causes vascular relaxations through release of endothelial relaxing factors including prostacyclin, nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). Bradykinin is metabolized by angiotensin converting enzyme (ACE) and ACE inhibition enhances bradykinin relaxations. Our goal was to characterize the role of bradykinin receptors and endothelial factors in ACE inhibitor-enhanced relaxations in bovine coronary arteries. In U46619 preconstricted arteries, bradykinin (10-11-10-8m) caused concentration-dependent relaxations (maximal relaxation ≥100%, log EC50=-9.8±0.1). In the presence of the NO synthase inhibitor, N-nitro-L-arginine (L-NA, 30 μm) and the cyclooxygenase inhibitor, indomethacin (10 μm), relaxations were reduced by an inhibitor of EET synthesis, miconazole (10 μm) (maximal relaxation=55±10%). Bradykinin relaxations were inhibited by the bradykinin 2 (B2) receptor antagonist, D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin (1 μm) (log EC50=-8.5±0.1) but not altered by the B1 receptor antagonist, des-Arg9[Leu8]bradykinin (1 μm). Mass spectrometric analysis of bovine coronary artery bradykinin metabolites revealed a time-dependent increase in bradykinin (1-5) and (1-7) suggesting metabolism by ACE. ACE inhibition with captopril (50 μm) enhanced bradykinin relaxations (log EC50=-10.3±0.1). The enhanced relaxations were eliminated by L-NA or the B1 receptor antagonist but not the B2 receptor antagonist. Our results demonstrate that ACE inhibitor-enhanced bradykinin relaxations of bovine coronary arteries occur through endothelial cell B1 receptor activation and NO.
Author List
Gauthier KM, Cepura CJ, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin-Converting Enzyme InhibitorsAnimals
Bradykinin
Captopril
Cattle
Coronary Vessels
Drug Synergism
Endothelium, Vascular
In Vitro Techniques
Muscle Relaxation
Nitric Oxide
Receptor, Bradykinin B1