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Angiotensin II type 1 receptor 1166A/C polymorphism in association with blood pressure response to exogenous angiotensin II
Cited 12 time in
Web of Science
Cited 11 time in Scopus
- Authors
- Issue Date
- 2006-12-06
- Publisher
- Springer Verlag
- Citation
- Eur J Clin Pharmacol. 2007 Jan;63(1):17-26. Epub 2006 Dec 5.
- Keywords
- Adult ; Angiotensin II/*pharmacology ; Angiotensin II Type 1 Receptor Blockers/pharmacology ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Receptor, Angiotensin, Type 1/agonists/*genetics ; Renin-Angiotensin System/physiology ; Tetrazoles/pharmacology ; Valine/analogs & derivatives/pharmacology ; Blood Pressure ; Polymorphism, Single Nucleotide
- Abstract
- BACKGROUND: The angiotensin II type 1 receptor (AT1R) 1166A/C polymorphism is reported to be implicated in cardiovascular diseases. The association between the 1166A/C polymorphism and diastolic blood pressure (DBP) changes in response to exogenous angiotensin II and valsartan was evaluated by pharmacokinetic and pharmacodynamic modeling. METHODS: Thirteen normotensive, healthy adults (six with the 1166A/A polymorphism and seven with 1166A/C) were enrolled in this clinical study. Angiotensin II was infused continuously over a 2-min period at four different rates (from 5 ng/kg/min and increased by 5 ng/kg/min) at 0 (before valsartan dosing), 2, 4, 8, 12, and 24 h after a single oral dose of valsartan (40 mg). BP was measured serially before and at the end of each rate of angiotensin II infusion. Plasma concentration-time profiles of valsartan were established over a 24-h period. We analyzed data using NONMEM and studied the relationship between the AT1R 1166A/C genotypes and BP responses. RESULTS: Plasma valsartan concentrations and DBP data best fitted into a two-compartment linear model and E(max) model (E(max) with baseline for angiotensin II and inhibitory E(max) for valsartan), respectively. The ED50 for angiotensin II in the subjects with 1166A/C [95% confidence interval (CI): 4.30 approximately 14.02 ng/kg/min] was significantly lower than in those with 1166A/A (95% CI: 14.23 approximately 28.77 ng/kg/min), while the E(max) for angiotensin II and EC50 for valsartan was similar in both genotype groups. CONCLUSIONS: These results suggest that exogenous human angiotensin II increases the BP more potently in subjects with 1166A/C than in those with 1166A/A.
- ISSN
- 0031-6970 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17146658
https://hdl.handle.net/10371/23384
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