Pressor effect of tonin in anephric animals

Tonin was injected intravenously to normal rats without effect on blood pressure. Twenty-four hours after bilateral nephrectomy, tonin produced a dose-dependent pressor effect in rats which was abolished by the angiotensin antagonist [Sar1-Ala8]-angiotensin II. Vascular response to angiotensin II was slightly increased after nephrectomy. Plasma angiotensin II increased significantly after injection of tonin and disappeared biexponentially with a half-life of less than 1 min for the fast component and 9 min for the slow component. The change in plasma angiotensin II correlated with the elevation in mean blood pressure. No difference in inhibitory power of plasma on tonin activity could be shown between intact and nephrectomized rats. In vitro, the initial velocity of generation of angiotensin II by tonin acting on plasma increased after addition of semipurified rat renin substrate and was significantly greater in plasma of nephrectomized rats. In nephrectomized rabbits, but not in intact ones, a dose-dependent pressor effect was produced by tonin. These data demonstrate the in vivo production of angiotensin II by tonin in an animal model with elevated substrate levels. Together with the in vitro data, these results suggest a role for substrate concentration in the expression of tonin enzymatic activity in vivo.