Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique |
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Authors: | B Gudo J Nussberger J Bohlender |
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Institution: | 1. Faculté de médecine, université Otto-von-Guericke, Leipziger Str. 44, 39120 Magdebourg, Allemagne;2. Département de médecine, centre hospitalier universitaire vaudois (CHUV), avenue Pierre-Decker 5, 1011 Lausanne, Suisse;3. KMG Klinikum Havelberg, Domherrnstr. 10, 39350 Havelberg, Allemagne;4. Institut de biologie cellulaire, université de Berne, Baltzerstrasse 4, 3012 Berne, Suisse |
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Abstract: | AimGenetic 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 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.MethodsMale 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).ResultsAt baseline, transgenic rats had +18 mmHg 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).ConclusionIncreased 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. |
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Keywords: | Angiotensinogè ne Plasma Hypertension arté rielle C&oelig ur Rat Transgé nique Gè ne Angiotensine Monoxyde d&rsquo azote L-NAME |
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