NO-dependent blood pressure regulation in RGS2-deficient mice

Michael Obst, Jens Tank, Ralph Plehm, Kendall J. Blumer, Andrè Diedrich, Jens Jordan, Friedrich C. Luft, Volkmar Gross

Research output: Contribution to journalArticle

32 Scopus citations

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 ω-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.

Original languageEnglish
Pages (from-to)R1012-R1019
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume290
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Autonomic nervous system
  • Baroreflex
  • Blood pressure
  • Nitric oxide-guanosine 3′-cyclic monophosphate pathway
  • Regulator of G protein signaling 2-deficient mice
  • Spectral analysis

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