Overexpression of a mutant AT1 receptor in mice significantly attenuated AngII-induced hypertension (by 20 mm Hg at day 14) and reduced cardiac hypertrophy (HW/BW ratio 0.416% vs 0.441%).
Does overexpression of a mutant AT1 receptor attenuate AngII-induced hypertension and cardiac hypertrophy in mice?
Overexpression of a mutant AT1 receptor attenuates AngII-induced hypertension and cardiac hypertrophy by diminishing Akt and RhoA activation.
Mean Difference: 20
Absolute Event Rate: 0.416% vs 0.441%
BACKGROUND: The angiotensin II (AngII) type 1 receptor (AT1) regulates cardiovascular function by activating various signal pathways. The purpose of this study was to evaluate the effects of a mutant AT1 receptor on AngII-responding blood pressure and cardiac hypertrophy in conjunction with altered AngII activation of RhoA and Akt. METHODS: A mutant AT1 receptor was constructed and overexpressed in C57BL mice using a ubiquitous-expression vector pCAGGS. The phenotype and signal transduction of the transgenic (TG) mice were compared with the wild-type (WT) mice. RESULTS: The TG mice showed a similar baseline phenotype as WT mice, but their blood pressure in response to continuous AngII infusion was significantly lower, as measured on days 3, 4, 7, and 14, with a difference of 20 mm Hg by day 14. There was also a significantly larger heart-to-total-body-weight ratio in the WT mice, whose heart weight (HW) was 0.441 +/- 0.008% of total body weight (BW) compared to the TG mice at 0.416 +/- 0.008%. Aortic endothelial cells isolated from these TG mice displayed an altered signaling profile, such as diminished activation of Akt and RhoA in response to AngII. In contrast, Galphaq coupling and ERK/JNK activation did not change. CONCLUSION: The expression of an AT1 mutant receptor in the presence of WT receptor can effectively modulate AngII-effected signaling. Furthermore, the elimination of Akt and RhoA activation by AngII significantly reduces but does not eliminate its hypertensive effect.
Ahmad et al. (Thu,) conducted a other in Angiotensin II-induced hypertension and cardiac hypertrophy. Overexpression of a mutant AT1 receptor vs. Wild-type mice was evaluated on Blood pressure and heart-to-total-body-weight ratio in response to continuous AngII infusion (difference of 20 mm Hg by day 14). Overexpression of a mutant AT1 receptor in mice significantly attenuated AngII-induced hypertension (by 20 mm Hg at day 14) and reduced cardiac hypertrophy (HW/BW ratio 0.416% vs 0.441%).