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Influence of elevated renin substrate on angiotensin II and arterial blood pressure in conscious mice
Author(s) -
Cholewa Brian C.,
Mattson David L.
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.030015
Subject(s) - renin–angiotensin system , blood pressure , plasma renin activity , bolus (digestion) , medicine , renin inhibitor , endocrinology , angiotensin ii , mean arterial pressure , hemodynamics , chemistry , anesthesia , heart rate
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.