cGMP-dependent protein kinase mediates NO-but not acetylcholine-induced dilations in resistance vessels in vivo

Michael Koeppen, Robert Feil, Daniel Siegl, Susanne Feil, Franz Hofmann, Ulrich Pohl, Cor De Wit*

*Corresponding author for this work
60 Citations (Scopus)


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 cGK -/- 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 Ca 2+-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.

Original languageEnglish
Issue number6
Pages (from-to)952-955
Number of pages4
Publication statusPublished - 12.2004

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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