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| Content Provider | PubMed Central |
|---|---|
| Author | Dendorfer, Andreas Folkers, Verena Klinger, Matthias Wolfrum, Sebastian Dominiak, Peter |
| Copyright Year | 2003 |
| Abstract | The high efficacy of ACE inhibitors to potentiate the actions of kinins might be explained by a hypothetical compartment in which B2-receptors are colocalized with kinin degrading enzymes. To demonstrate the functional consequence of such a compartment we compared the myocardial uptake and the persistence of action of bradykinin under the influence of kininase inhibitors. Bradykinin-induced vasodilation and uptake of tritiated bradykinin were studied in perfused rat hearts during inhibition of ACE and aminopeptidase P. B2-receptors were localized by immuno-gold labelling and electron-microscopy. The EC50 of bradykinin-induced vasodilation (5.1±0.8 nM) was shifted to 14 fold lower concentrations during inhibition of both kininases. The maximum persistence of vasodilation after termination of bradykinin application (half-life 112±20 s) was increased by kininase inhibitors to 398±130 s. This prolongation was reversed when B2-receptors were blocked simultaneously with the termination of bradykinin infusion. Tritiated bradykinin (perfused for 1 min) was partially (1.7±0.24%) retained by the myocardium and consecutively released with a half-life of 70±9 s. Kinin uptake was increased during kininase inhibition (7.7±2.6%), and was normalized by HOE 140 (2.0±0.34%), or when a tritiated B2-receptor antagonist (NPC 17731) was used as label. B2-receptors were localized in plasmalemmal and cytosolic vesicles of capillary endothelium. Bradykinin is locally incorporated and can associate with B2-receptors repeatedly when kinin breakdown is inhibited. This is the kinetic and functional consequence of a colocalization of kininases and B2-receptors in a compartment constituted by endothelial membrane vesicles. |
| Related Links | http://dx.doi.org/10.1038/sj.bjp.0705036 |
| Starting Page | 310 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 138 |
| Language | English |
| Publisher Date | 2003-01-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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