Journal
CIRCULATION
Volume 105, Issue 16, Pages 1921-1927Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000014684.75359.68
Keywords
angiotensin; genetics; hypertension; kidney; renin
Funding
- NCRR NIH HHS [M01 RR 02635, M01 RR 00064] Funding Source: Medline
- NHLBI NIH HHS [HL-47651, HL-59424, HL-55000] Funding Source: Medline
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Background-Renovascular and adrenal responses to infused angiotensin II (Ang II) are intermediate phenotypes that may indirectly reflect tissue renin-angiotensin system activity. We examine herein angiotensinogen (AGT) as a candidate Gene to help elucidate potential mechanisms for previously reported AGT linkage and association studies. Methods and Results-Renal plasma flow and plasma aldosterone were measured before and after a 45-minute infusion of Ang Il (3 ng - kg(-1) - min(-1)) in 190 hypertensive patients who were on carefully controlled high- and low-salt diets. Reduced renal vascular (P=0.0002) and adrenal (P=0.002) responses to infused exogenous Ang 11 were associated with e the AGT - 6A allele. In multiple logistic regression, greater body mass index, lower basal renal plasma flow, and higher diastolic blood pressure together with AGT -6A genotype were associated with lower renal vascular response. In contrast, only male sex and AGT -6A genotype were associated with lower adrenal response. When both the renal and adrenal responses to Ang 11 were in the lowest tertile, the AGT -6AA genotype was present in 55.6%; in contrast, when both responses were in the upper 2 tertiles, the -6AA genotype was present in only 17.8% (P=0.001). Conclusions-A clear association between AGT genotype and response to infused Ang II was demonstrated for both the renal vasculature and the adrenal, consistent with the hypothesis that the AGT -6A genotype results in increased tissue expression of angiotensinogen and Ang II.
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