Influence of elevated renin substrate on angiotensin II and arterial blood pressure in conscious mice

The present experiments were performed to determine the influence of intravenous administration of renin substrate on plasma angiotensin II levels and mean arterial blood pressure in conscious C57BL/6J mice. Mice with chronic indwelling femoral arterial and venous catheters were acutely or chronically administered intravenous doses of a synthetic peptide corresponding to the 14 amino acids on the N-terminal of angiotensinogen. A dose-dependent increase in arterial blood pressure was observed as the intravenous bolus dose of the renin substrate was increased from 0.18 to 180 nmol kg^-1 with a maximal increase in pressure of 40 ± 3 mmHg achieved following administration of the 18 nmol kg^-1 bolus (n = 11). Additional experiments demonstrated that a sustained intravenous infusion of the renin substrate led to a long-term increase in arterial blood pressure. The continuous infusion of renin substrate at 0.05 nmol kg^-1 min^-1 for 3 days did not alter arterial blood pressure from the control level of 119 ± 5 mmHg (n = 5); however, arterial blood pressure significantly increased to 129 ± 6 mmHg with an infusion rate of 0.5 nmol kg^-1 min^-1 and further increased to 141 ± 3 mmHg when the renin substrate infusion was increased to 5.0 nmol kg^-1 min^-1. Finally, the infusion of renin substrate at 5.0 nmol kg^-1 min^-1 resulted in a significant increase in plasma angiotensin II concentration from 34 ± 6 pg ml^-1 in vehicle-infused mice to 288 ± 109 pg ml^-1. These results demonstrate that modulation of the circulating level of angiotensinogen can alter the plasma angiotensin II level and arterial blood pressure in normal animals.