[Variability of plasma angiotensinogen levels and risk of hypertension in a transgenic rat model]

Ann Cardiol Angeiol (Paris). 2014 Jun;63(3):124-7. doi: 10.1016/j.ancard.2014.04.017. Epub 2014 Apr 30.
[Article in French]

Abstract

Aim: Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods: Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n=3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results: At baseline, transgenic rats had +18mmHg higher bood pressure and -8% lower body weight compared to non-transgenic rats (P<0.05) without significant changes for the vehicle groups throughout the study (P>0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P<0.05) in transgenic and +25%, +5.3% and +6.7% (P>0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P>0.05).

Conclusion: Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.

Keywords: Angiotensin; Angiotensine; Angiotensinogen; Angiotensinogène; Cœur; Experimental; Gene; Gène; Heart; Hypertension; Hypertension artérielle; L-NAME; Monoxyde d’azote; Nitric oxide; Plasma; Rat; Transgenic; Transgénique.

Publication types

  • Comparative Study
  • English Abstract

MeSH terms

  • Angiotensinogen / blood*
  • Animals
  • Blood Pressure / drug effects*
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hypertension / drug therapy
  • Hypertension / enzymology*
  • Hypertension / physiopathology
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Rats
  • Rats, Transgenic

Substances

  • Enzyme Inhibitors
  • Angiotensinogen
  • NG-Nitroarginine Methyl Ester