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

Item Type:Article
Title:Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice
Creators Name:Hercule, H.C., Tank, J., Plehm, R., Wellner, M., da Costa Goncalves, A.C., Gollasch, M., Diedrich, A., Jordan, J., Luft, F.C. and Gross, V.
Abstract: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.
Keywords:Angiotensin II, Animal Disease Models, Arterioles, Baroreflex, Blood Pressure, Endothelin-1, Epinephrine, Heart Rate, Hypertension, Norepinephrine, Phenylephrine, RGS Proteins, Type 1 Angiotensin Receptor, Type 2 Angiotensin Receptor, Vasoconstriction, Vasoconstrictor Agents, Animals, Mice
Source:Experimental Physiology
Publisher:Blackwell Publishing
Page Range:1014-1022
Date:November 2007
Official Publication:https://doi.org/10.1113/expphysiol.2007.038240
PubMed:View item in PubMed

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