NO-dependent blood pressure regulation in RGS2-deficient mice.
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.
Obst
Michael
M
Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Tank
Jens
J
Plehm
Ralph
R
Blumer
Kendall J
KJ
Diedrich
Andrè
A
Jordan
Jens
J
Luft
Friedrich C
FC
Gross
Volkmar
V
D000818:Animals; D001158:Arteries / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004837:Epinephrine / Q000652:urine; D006339:Heart Rate / Q000187:drug effects*; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D020710:RGS Proteins / Q000235:genetics*; D014661:Vasoconstriction
D020710:RGS Proteins; C087182:RGS2 protein, human; D001285:Atropine; D052248:Nitric Oxide Synthase Type I; D008790:Metoprolol; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin; D004837:Epinephrine