Angiotensin II is the major peptide of the renin-angiotensin system RAS and plays a crucial role in the cardiovascular homeostasis. Dysfunction of the RAS can lead to hypertension. Recently, non-peptide AT1 antagonists have been developed and they have an antihypertensice effect. Pharmacological tests with these antagonists showed their insurmountable inhibition, i.e. they did not only produced a rightward shift of the angiotensin II induced dose-response curve, but they also lowered the maximal response. Tests in our laboratorium showed that this type of inhibition is due to slow dissociation of the antagonistreceptor complex. Inthis project we want to investigate the clinical and physiological relevance of this type of inhibition. Therfore we will use cell lines of target organs of the RAS which contain endogene AT1 receptors. On these cells studies will be performed to investigate the binding characteristics of the AT1 receptor antagonists and their inhibition on angiotensin II mediated physiological responses. the next step is to measure the in vivo receptor occupancy and plasmabinding after oral administration of the antagonists to rats.
|Effective start/end date||1/10/99 → 30/09/03|
Flemish discipline codes
- Basic sciences
- Pharmaceutical sciences