Transient inhibition of angiotensinogen production in transgenic mice bearing an antisense angiotensinogen gene.

Angiotensinogen is the precursor of the biologically active hormone angiotensin II. Enzyme kinetic parameters suggest that concentrations of plasma angiotensinogen are rate limiting in the renin reaction. It is therefore assumed that a decrease in angiotensinogen synthesis in vivo would result in a decrease in angiotensin II plasma levels and then of blood pressure. To test this hypothesis, we generated a transgenic mouse line that carries an inducible antisense angiotensinogen gene. Transient inhibition of angiotensinogen synthesis could be demonstrated in these transgenic animals. However, the amounts of liver angiotensinogen message and plasma angiotensinogen concentrations were rapidly back to levels observed in control animals.