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NO-dependent blood pressure regulation in RGS2-deficient mice

Item Type:Article
Title:NO-dependent blood pressure regulation in RGS2-deficient mice
Creators Name:Obst, M., Tank, J., Plehm, R., Blumer, K.J., Diedrich, A., Jordan, J., Luft, F.C. and Gross, V.
Abstract:The regulator of G protein signaling (RGS) 2, a GTPase-activating protein, is activated via the nitric oxide (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 N(omega)-nitro-l-arginine methyl ester (l-NAME, 5 mg l-NAME/10 ml tap water)-treated RGS2-deficient (RGS2(-/-)) and RGS2-sufficient (RGS2(+/+)) mice and assessed autonomic function. Without l-NAME, RGS2(-/-) mice showed during day and night a similar increase of MAP compared with controls. l-NAME treatment increased MAP in both strains. nNOS is involved in this l-NAME-dependent blood pressure increase, since 7-nitroindazole increased MAP by 8 and 9 mmHg (P < 0.05) in both strains. The l-NAME-induced MAP increase of 14-15 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 vs. 17 +/- 2 mmHg; P < 0.05). Urinary norepinephrine and epinephrine excretion was higher in RGS2(-/-) than in RGS2(+/+) mice. The MAP decrease after prazosin was more pronounced in l-NAME-RGS2(-/-). HR variability parameters [root mean square of successive differences (RMSSD), low-frequency (LF) power, and high-frequency (HF) power] and baroreflex sensitivity were increased in RGS2(-/-). Atropine and atropine plus 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.
Keywords:Arteries, Atropine, Baroreflex, Blood Pressure, Epinephrine, Heart Rate, Metoprolol, Knockout Mice, NG-Nitroarginine Methyl Ester, Nitric Oxide Synthase Type I, Prazosin, RGS Proteins, Vasoconstriction, Animals, Mice
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
Publisher:American Physiological Society
Page Range:R1012-R1019
Date:1 April 2006
Official Publication:https://doi.org/10.1152/ajpregu.00288.2005
PubMed:View item in PubMed

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