RGS2 is a mediator of nitric oxide action on blood pressure and vasoconstrictor signaling.
The nitric oxide (NO)-cGMP pathway regulates vascular tone and blood pressure by mechanisms that are incompletely understood. RGS2, a GTPase-activating protein for Gqalpha that is critical for blood pressure homeostasis, has been suggested to serve as an effector of the NO-cGMP pathway that promotes vascular relaxation based on studies of aortic rings in vitro. To test this hypothesis and its relevance to blood pressure control, we determined whether RGS2 functions as an NO effector in smooth muscle of the resistance vasculature. We report that 1) the ability of the NO donor sodium nitroprusside to reduce blood pressure is impaired in RGS2-/- mice, 2) vasopressin-triggered Ca2+ transients are augmented in smooth muscle cells from resistance arteries of RGS2-/- mice, and 3) cGMP analogs fail to inhibit vasopressin-triggered Ca2+ transients in smooth muscle cells from resistance arteries of RGS2-/- mice even though cGMP-dependent protein kinase (PKG)1alpha and PKG1beta are expressed and activated normally. These results indicated that the NO-cGMP pathway uses RGS2 as a novel downstream effector to promote vascular relaxation by attenuating vasoconstrictor-triggered Ca2+ signaling in vascular smooth muscle cells. Genetic or epigenetic impairment of this mechanism may contribute to the development of hypertension, and augmenting it pharmacologically may provide a novel means of treating this disease.
Sun
Xiaoguang
X
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Kaltenbronn
Kevin M
KM
Steinberg
Thomas H
TH
Blumer
Kendall J
KJ
D000818:Animals; D001013:Aorta, Thoracic; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D020710:RGS Proteins; C105345:Rgs2 protein, mouse; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D009569:Nitric Oxide