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

• Published in: Experimental physiology 2005-07, Vol.90 (4), p.607
• Main Authors: Cholewa, Brian C, Mattson, David L
• Format: Article
• Language: English
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2005.030015

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.