ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries
| Autor: | Cody Cepura, Kathryn M. Gauthier, William B. Campbell |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Captopril Endothelium medicine.drug_class Muscle Relaxation Clinical Biochemistry Bradykinin Angiotensin-Converting Enzyme Inhibitors Prostacyclin In Vitro Techniques Nitric Oxide Receptor Bradykinin B1 Biochemistry Article Nitric oxide chemistry.chemical_compound Internal medicine medicine Animals Bradykinin receptor Molecular Biology biology Chemistry Drug Synergism Angiotensin-converting enzyme Receptor antagonist Coronary Vessels Endocrinology medicine.anatomical_structure biology.protein Cattle Endothelium Vascular medicine.drug |
| Zdroj: | bchm. 394:1205-1212 |
| ISSN: | 1437-4315 1431-6730 |
| Popis: | 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 (10-11-10-8 m) 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. |
| Databáze: | OpenAIRE |
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