title: Angiotensinogen genotype affects renal and adrenal responses to angiotensin II in essential hypertension.
abstract: 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.
  
  
  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.
authors: Cardiovascular Genetics, Cardiology Division, University of Utah, Salt Lake City, UT, USA. paul@ucvg.med.utah.edu
authors: Paul N
authors: PN
authors: Hopkins
authors: Steven C
authors: SC
authors: Hunt
authors: Xavier
authors: X
authors: Jeunemaitre
authors: Barbara
authors: B
authors: Smith
authors: Daniel
authors: D
authors: Solorio
authors: Naomi D L
authors: ND
authors: Fisher
authors: Norman K
authors: NK
authors: Hollenberg
authors: Gordon H
authors: GH
authors: Williams
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D000808:Angiotensinogen / Q000235:genetics*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017595:Renal Plasma Flow / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000808:Angiotensinogen; D000804:Angiotensin II; D000450:Aldosterone