Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0406810 (
NAME
)
13,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:NO-dependent blood pressure regulation in RGS2-deficient mice. 1626 76
G protein-coupled receptors (GPCRs) are expressed ubiquitously and involved in a variety of physiologic and pathologic processes. One of the key steps in the GPCR signaling cascade is the phosphorylation of the Galpha-subunit that triggers its dissociation from the Gbetagamma-subunit and from the receptor, allowing both G protein subunits to activate different downstream second messengers. Thereafter, Galpha hydrolyzes the attached guanosine triphosphate (GTP) to guanosine diphosphate (GDP) by its inherent enzymatic activity and terminates signaling. Small/connecting proteins that act as GTPase activating proteins (GAP) accelerate this process. Regulator of G protein signaling (RGS) proteins play a key role in the regulation of GPCRs, by acting as GAP and increasing the rate of GPCRs deactivation.
RGS2
affects GPCR-dependent and GPCR-independent pathways.
RGS2
-/- displayed an increase of blood pressure (BP) mainly by an increase of total peripheral resistance. After N(omega)-nitro-L-arginine methyl ester (L-
NAME
)
RGS2
-/- mice responded with a smaller BP increase during the day than
RGS2
+/+, suggesting an impaired NO signaling. Infusion of angiotensin II increased BP stronger in
RGS2
-/- compared with
RGS2
+/+. In summary, GPCR-dependent and GPCR-independent pathways are involved in BP changes of
RGS2
-/- mice. Interactions between GPCRs and
RGS2
represent a regulatory mechanism for fine-tuning of BP which may be important for hypertension and may be considered as a potentially novel drug target.
...
PMID:Fine tuning of blood pressure by the regulator of G protein signaling (RGS) 2. 2040 24
