The epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is involved in the regulation of cell proliferation, survival and differentiation. Pathophysiological effects of EGFR include cell transformation and tumorigenesis as well as parainflammatory dysregulation of tissue homeostasis leading to cardiovascular dysfunction and fibrosis.

To investigate the importance of EGFR in vascular smooth muscle cells (VSMC) we generated a mouse model with targeted deletion of the EGFR (EGFR^D/D/VSMC&CM, KO). Deletion of EGFR in VSMC and CM was confirmed by qPCR and EGF-responsiveness of the cells. To analyze the importance of the EGFR for the maintenance of the physiological blood pressure we performed tail cuff measurements on conscious animals and intravascular blood pressure measurements employing a Millar catheter.

Systolic blood pressure was not different in both genotypes, while diastolic blood pressure was lower in KO and blood pressure amplitude and stroke volume were increased, indicating a reduced peripheral resistance. Fromin vitrostudies it is supposed that the EGFR facilitates some of the effects of vasoactive substances like Angiotensin II (AngII). Therefore we infused anasthetized mice with 1mg//kg AngiotensinII and measured acute changes in blood pressure intravascular. AngII induced an identical maximal increase in systolic and diastolic blood pressure in both genotypes. However, blood pressure decrease significantly faster in KO animals making the effect of AngII less persistent.

In conclusion our data indicates that the EGFR in VSMC is necessary for the maintenance of physiological baseline blood pressure and mediates some of the pressurizing effects of AngIIin vivo.