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

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.