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


CONCLUSIONS
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.
Faculté de médecine, université Otto-von-Guericke, Leipziger Str. 44, 39120 Magdebourg, Allemagne.
B
B
Gudo
Département de médecine, centre hospitalier universitaire vaudois (CHUV), avenue Pierre-Decker 5, 1011 Lausanne, Suisse.
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J
Nussberger
Faculté de médecine, université Otto-von-Guericke, Leipziger Str. 44, 39120 Magdebourg, Allemagne; KMG Klinikum Havelberg, Domherrnstr. 10, 39350 Havelberg, Allemagne; Institut de biologie cellulaire, université de Berne, Baltzerstrasse 4, 3012 Berne, Suisse. Electronic address: juergen.bohlender@bluewin.ch.
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J
Bohlender
D000808:Angiotensinogen / Q000097:blood*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D055647:Rats, Transgenic
D004791:Enzyme Inhibitors; D000808:Angiotensinogen; D019331:NG-Nitroarginine Methyl Ester
Angiotensin; Angiotensine; Angiotensinogen; Angiotensinogène; Cœur; Experimental; Gene; Gène; Heart; Hypertension; Hypertension artérielle; L-NAME; Monoxyde d’azote; Nitric oxide; Plasma; Rat; Transgenic; Transgénique