Blood pressures, heart rate and locomotor activity during salt loading and angiotensin II infusion in protease-activated receptor 2 (PAR2) knockout mice

Abstract

Background. In this study we used radiotelemetry to measure hemodynamic variables and locomotor activity in conscious unrestrained male Protease-Activated Receptor 2 (PAR-2) knockout mice in order to provide a detailed assessment of their blood pressure phenotype. In addition we tested for an influence of PAR-2 on salt-sensitivity (8% versus 0.5% NaCl diet, 2.5 weeks) and angiotensin II-induced hypertension (1 μg Ile5-angiotensin II/kg/min versus 0.25 μl/h saline, 2 weeks). Results. Systolic arterial pressures of PAR-2 -/- (129 ± 1 mmHg, n = 21, P < 0.05) were statistically higher than those of C57BL/6J (124 ± 1 mmHg, n = 33) throughout the 24 h period under baseline conditions. Pulse pressures in PAR-2 -/- were also significantly elevated (33 ± 1 mmHg versus 30 ± 1 mmHg, P < 0.05), whereas diastolic arterial pressures were not. Heart rates in PAR-2 -/- were not significantly different than controls, with the exception that heart rate of PAR-2 -/- was 23 beats per min higher than controls (P < 0.001) during periods of nocturnal activity. The diurnal pattern and intensity of locomotor activity were not found to differ between strains. A high salt diet led to increased blood pressures, decreased heart rates, increased time spent active and decreased intensity levels of locomotor activity. Salt-induced changes in systolic and pulse pressures in PAR-2 -/- were less than in C57B/6J. Angiotensin II treatment increased pressures, decreased heart rates, decreased time spent active and decreased intensity levels of activity of PAR-2 -/-, all to the same extent as C57BL/6J. A trend of lower blood pressures during the middle period of angiotensin II treatment period was observed in individual PAR-2 -/-. Conclusion. The data indicated gene knockout of PAR-2 was associated with a modest change in blood pressure phenotype. PAR-2 -/- mice exhibited moderate elevation of systolic arterial and pulse pressures, yet no increased diastolic arterial pressure, no increased blood pressure responses to high salt diet and a subtle difference in the time course of the blood pressure responses to angiotensin II infusion. © 2008 McGuire et al; licensee BioMed Central Ltd.