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.