Altered heart rate and blood pressure variability in mice lacking the Mas protooncogene

Heart rate variability is a relevant predictor of cardiovascular risk in hu mans. A significant genetic influence on heart rate variability is suggeste d, although the genes involved are ill-defined. The Mas-protooncogene encod es a G-protein-coupled receptor with seven transmembrane domains highly exp ressed in testis and brain. Since this receptor is supposed to interact wit h the signaling of angiotensin II, which is an important regulator of cardi ovascular homeostasis, heart rate and blood pressure were analyzed in Mas-d eficient mice. Using a femoral catheter the blood pressure of mice was meas ured for a period of 30 min and 250 data values per second were recorded. T he mean values and range of heart rate and blood pressure were then calcula ted. Neither heart rate nor blood pressure were significantly different bet ween knockout mice and controls. However, high resolution recording of thes e parameters and analysis of the data by non-linear dynamics revealed signi ficant alterations in cardiovascular variability in Mas-deficient animals. In particular, females showed a strong reduction of heart rate variability. Furthermore, the data showed an increased sympathetic tone in knockout ani mals of both genders. The marked alterations detected in Mns-deficient mice of both genders suggest that the Mas-protooncogene is an important determi nant of heart rate and blood pressure variability.