Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice

Angiotensin II (Ang II) activates signalling pathways predominantly through the G-protein-coupled Ang II type 1 receptor (AT 1 R). The regulator of G protein signalling 2 (RGS2) is a negative G protein regulator. We hypothesized that RGS2 deletion changes blood pressure regulation by increasing the response to Ang II. To address this issue, we infused Ang II (0.5 mg kg −1 day −1 ) chronically into conscious RGS2 -deleted ( RGS2 −/− ) and wild-type ( RGS2 +/+ ) mice, measured mean arterial blood pressure and heart rate (HR) with telemetry and assessed vasoreactivity and gene expression of AT 1A , AT 1B and AT 2 receptors. Angiotensin II infusion increased blood pressure more in RGS2 −/− than in RGS2 +/+ mice, while HR was not different between the groups, indicating a resetting of the baroreceptor reflex. Urinary catecholamine excretion was similar in Ang II-infused RGS2 −/− and RGS2 +/+ mice, indicating a minor role of sympathetic tone for blood pressure differences. Myogenic tone and vasoreactivity in response to Ang II, endothelin-1 and phenylephrine were increased in isolated renal interlobar arterioles of RGS2 −/− mice compared with RGS2 +/+ mice. The AT 1A , AT 1B and AT 2 receptor gene expression was not different between RGS2 −/− and RGS2 +/+ mice. Our findings suggest that RGS2 deletion promotes Ang II-dependent hypertension primarily through an increase of myogenic tone and vasoreactivity, probably by sensitization of AT 1 receptors.