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 II (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 II were associated with 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 II 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.
|Number of pages||7|
|Publication status||Published - 23 Apr 2002|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)