Received January 21, 2005
Revised February 14, 2005
Accepted after revision April 12, 2005

¹ Medical College of Wisconsin

^* To whom correspondence should be addressed. E-mail: dmattson{at}mcw.edu.

	Abstract

The present experiments were performed to determine the influence of intravenous administration of renin substrate on plasma angiotensin II 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 with a maximal increase in pressure of 40±3 mmHg achieved following administration of the 18 nmol/kg 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/min for three 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/min and further increased to 141±3 mmHg when the renin substrate infusion was increased to 5.0 nmol/kg/min. Finally, the infusion of renin substrate at 5.0 nmol/kg/min resulted in a significant increase in plasma angiotensin II from 34±6 in vehicle-infused mice to 288±109 pg/ml. These results demonstrate that modulation of the circulating level of angiotensinogen can alter plasma angiotensin II and arterial blood pressure in normal animals.

Key Words: Angiotensin, Blood pressure, Renin