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1 Max Delbruck Center for Molecular Medicine, Berlin, Germany
2 Medical Faculty of the Charite, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Berlin, Germany
3 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
4 Autonomic Dysfunction Service, Vanderbilt University, Nashville, TN, USA
5 Max Delbruck Center for Molecular Medicine, Berlin, Germany; Medical Faculty of the Charite, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: vgross{at}mdc-berlin.de.
The regulator of G protein signaling (RGS)2, a GTPase-activating protein, is activated via the NO-cGMP pathway and thereby may influence blood pressure regulation. To test that notion, we measured mean arterial blood pressure (MAP) and heart rate (HR) with telemetry in L-NAME (5 mg L-NAME/10 ml tap water) treated RGS2 -/- and RGS2 +/+ mice and assessed autonomic function. Without L-NAME, RGS2-/- mice showed during day and night a similar increase of MAP compared to controls. L-NAME treatment increased MAP in both strains. nNOS is involved in this L-NAME dependent blood pressure increase, since 7-nitroindazole (7-NI) increased MAP by 8 and 9 mmHg (p< 0.05) in both strains. The L-NAME-induced MAP increase of 14 to 15 mmHg during night was similar in both strains. However, the L-NAME induced MAP increase during the day was smaller in RGS2 -/- than in RGS2 +/+ (11±1 mmHg vs. 17±2 mmHg; p< 0.05). Urinary norepinephrine and epinephrine excretion was higher in RGS2 -/- than in RGS2 +/+ mice. The MAP decrease following prazosin was more pronounced in L-NAME-RGS2-/-. HR variability parameters (RMSSD, LF, HF) and baroreflex sensitivity (BRS-LF) were increased in RGS2 -/-. Atropine and atropine&metoprolol markedly reduced RMSSD, LF, and HF. Our data suggest an interaction between RGS2 and the NO-cGMP pathway. The blunted L-NAME response in RGS2 -/- during the day suggests impaired NO signaling. The MAP increases during the active phase in RGS2 -/- mice may be related to central sympathetic activation and increased vascular adrenergic responsiveness.
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