title: Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice.
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.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Hantz C
authors.initials: HC
authors.lastname: Hercule
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Maren
authors.initials: M
authors.lastname: Wellner
authors.forename: Andrey C
authors.initials: AC
authors.lastname: da Costa Goncalves
authors.forename: Maik
authors.initials: M
authors.lastname: Gollasch
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000502:physiology; D004837:Epinephrine / Q000652:urine; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000652:urine; D010656:Phenylephrine / Q000494:pharmacology; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D020710:RGS Proteins; C087182:RGS2 protein, human; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D009638:Norepinephrine; D004837:Epinephrine