TRANSIENT INHIBITION OF ANGIOTENSINOGEN PRODUCTION IN TRANSGENIC MICEBEARING AN ANTISENSE ANGIOTENSINOGEN GENE

Angiotensinogen is the precursor of the biologically active hormone an giotensin 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 viv o 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. T ransient inhibition of angiotensinogen synthesis could be demonstrated in these transgenic animals. However, the amounts of liver angiotensi nogen message and plasma angiotensinogen concentrations were rapidly b ack to levels observed in control animals.