Angiotensinogen genotype affects renal and adrenal responses to angiotensin II in essential hypertension

Circulation. 2002 Apr 23;105(16):1921-7. doi: 10.1161/01.cir.0000014684.75359.68.


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 x kg(-1) x 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adrenal Glands / drug effects
  • Adult
  • Aged
  • Aldosterone / blood
  • Angiotensin II / pharmacology*
  • Angiotensinogen / genetics*
  • Antihypertensive Agents / pharmacology*
  • Female
  • Genotype
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy
  • Hypertension / genetics*
  • Kidney / blood supply
  • Kidney / drug effects
  • Male
  • Middle Aged
  • Models, Biological
  • Renal Plasma Flow / drug effects


  • Antihypertensive Agents
  • Angiotensinogen
  • Angiotensin II
  • Aldosterone