S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Clinical Pharmacology (협동과정-임상약리학전공) Journal Papers (저널논문_협동과정-임상약리학전공)
Angiotensin II type 1 receptor 1166A/C polymorphism in association with blood pressure response to exogenous angiotensin II
- Lim, Hyeong-Seok; Cho, Joo-Youn; Oh, Dal-Seok; Chung, Jae-Yong; Hong, Kyoung-Sup; Bae, Kyun-Seop; Yu, Kyung-Sang; Lee, Kyung-Hoon; Jang, In-Jin; Shin, Sang-Goo
- Issue Date
- Springer Verlag
- Eur J Clin Pharmacol. 2007 Jan;63(1):17-26. Epub 2006 Dec 5.
- Adult; Angiotensin II/*pharmacology; Angiotensin II Type 1 Receptor Blockers/pharmacology; *Blood Pressure; Female; Gene Frequency; Genotype; Humans; Male; *Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1/agonists/*genetics; Renin-Angiotensin System/physiology; Tetrazoles/pharmacology; Valine/analogs & derivatives/pharmacology
- 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.
- 0031-6970 (Print)
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