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Objective: Long-term cardiac output measurements in non-anesthetized mice are now possible. We used this technology to study two different hypertensive models in mice., Design: We combined telemetric blood pressure and heart rate recordings with Doppler flow probe cardiac output measurements in mice during treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) and deoxycorticosterone acetate (DOCA)-salt., Method: The mice received a flowprobe around the ascending aorta and, 10-18 days later, blood pressure telemetry. After recovery, baseline values were recorded and the mice were given L-NAME (5 mg/10 ml tap water), L-NAME followed by valsartan (50 mg/kg per day per gavage), or DOCA-salt (50 mg DOCA-pellet, 0.9% saline to drink, uninephrectomy). Mean arterial pressure, heart rate, stroke volume and cardiac output were recorded daily and total peripheral resistance was calculated., Results: L-NAME resulted in an abrupt increase in mean arterial pressure caused solely by an increase in total peripheral resistance. Cardiac output was decreased. Valsartan treatment decreased blood pressure and total peripheral resistance, while cardiac output was restored to normotensive values. DOCA-salt required 3 days before hypertension developed. Contrary to the volume expansion, increased cardiac output, autoregulation hypothesis, the blood pressure increase was only associated with increased total peripheral resistance, while cardiac output was not changed., Conclusion: Both L-NAME and DOCA-salt increased blood pressure by increasing total peripheral resistance. Comprehensive hemodynamics can be done in non-anesthetized, free-moving mice. The methods provide new perspectives for studying mouse models in the long-term.

Background: The role of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in cardiac hypertrophy and fibrosis is incompletely understood. The availability of AT2 receptor-deficient mice (AT2 -/y) makes it possible to study the effects of AT1 receptors without the confounding influence of AT2 receptor activity., Objective: To test the hypothesis that the AT2 receptor affords protection from left ventricular hypertrophy and fibrosis in chronic hypertension induced by N-nitro-L-arginine methyl ester (L-NAME)., Design: Four groups of mice were studied over a period of 3 weeks: AT2 -/y mice with and without L-NAME, and AT2 +/y mice with and without L-NAME., Methods: Blood pressure and heart rate were monitored by telemetry in groups of AT2 +/y and AT2 -/y mice for 4 weeks. L-NAME groups received the compound in drinking water for the last 3 weeks. We determined left ventricular AT1 receptor expression, cardiac hypertrophy and fibrosis, with and without L-NAME treatment. We used a miniaturized conductance-manometer system to measure pressure-volume loops at the time when the animals were killed., Results: AT2 -/y mice treated with L-NAME showed worse left ventricular hypertrophy, more perivascular fibrosis and greater concentrations of brain natriuretic peptide than did AT2 +/y mice treated with L-NAME. The end-systolic pressure-volume relationship, an index of left ventricular contractility, was decreased in AT2 -/y mice treated with L-NAME., Conclusions: The AT2 receptor is not essential for development of L-NAME-induced cardiac hypertrophy, fibrosis and concomitant changes in left ventricular performance. In contrast, the AT2 receptor offers a protective effect.