Effect of the angiotensinogen genotype on experimental hypertension in mice.
Polymorphisms of the angiotensinogen (Agt) gene may affect blood pressure. We used a mouse model to test for the role of the Agt genotype in low-renin or high-renin forms of hypertension. Mice bearing one, two, three, or four copies of the Agt gene underwent renal artery clipping to induce high-renin two-kidney, one-clip renovascular hypertension (2K1C), or uninephrectomy, salt loading, and application of deoxycorticosterone-acetate (DOCA) pellets to induce low-renin mineralocorticoid hypertension. Appropriate control animals were also studied. Blood pressure was measured by tail cuff as well as by direct intra-arterial recordings. There was a small effect of the Agt genotype on baseline blood pressure before induction of hypertension. The extent of 2K1C hypertension was not affected by the genotype. In contrast, there was a marked gene-dose effect on DOCA-hypertension (21.2 mmHg over all genotypes). Treatment of DOCA mice with the angiotensin II type 1 receptor antagonist abolished the genotype effect on blood pressure and left ventricular hypertrophy. There was a trend towards less suppression of endogenous aldosterone by DOCA treatment with increasing number of Agt gene copies. We conclude that the Agt genotype exerts a marked effect on blood pressure in a low-renin form of hypertension but no effect in the face of stimulated renin, at least in mice.
Handtrack
Claudia
C
Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany.
Cordasic
Nada
N
Klanke
Bernd
B
Veelken
Roland
R
Hilgers
Karl F
KF
D000808:Angiotensinogen / Q000235:genetics* / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D005838:Genotype; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D012084:Renin-Angiotensin System / Q000235:genetics*
D000808:Angiotensinogen