title: cGMP-dependent protein kinase mediates NO- but not acetylcholine-induced dilations in resistance vessels in vivo.
abstract: cGMP and cGMP-dependent protein kinase type I (cGKI) mediate the dilation of large vessels in response to NO and acetylcholine (ACh). However, the physiological significance of the NO/cGMP/cGKI pathway in resistance vessels is controversial. Here, we analyzed NO- and ACh-induced dilations of arterioles in cGKI-deficient (cGKI-/-) or endothelial NO synthase-deficient (eNOS-/-) mice. Mean arterial pressure was similar in cGKI-/- and wild-type mice (105 mm Hg). Pressure drops in response to intracarotid bolus application of the NO donor sodium nitroprusside (SNP) were almost abolished in cGKI-/- mice, whereas ACh-induced pressure decreases remained intact in cGKI-/- and eNOS-/- mice. The direct observation of arterioles in the cremaster muscle by intravital microscopy showed impaired SNP-induced dilations in cGKI-/- mice (by 80%) and normal ACh-induced dilations in cGKI-/- and eNOS-/- mice. ACh-induced dilations in eNOS-/- mice were attenuated by iberiotoxin (by 50%), indicating that they were mediated in part by Ca2+-activated K+ channels, but not by inhibitors of cyclooxygenase or p450-monooxygenases. We conclude that cGMP and cGKI are the major effectors of NO to induce acute dilations of murine resistance vessels. However, the NO/cGMP/cGKI pathway is not essential for ACh-induced dilation of arterioles and for basal blood pressure regulation in mice.
authors.affiliation: Physiologisches Institut, Universität Lübeck, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koeppen
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Daniel
authors.initials: D
authors.lastname: Siegl
authors.forename: Susanne
authors.initials: S
authors.lastname: Feil
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pohl
authors.forename: Cor
authors.initials: C
authors.lastname: de Wit
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; D000109:Acetylcholine