on October 25, 2004
Published online before print October 25, 2004, doi: 10.1161/01.HYP.0000147661.80059.ca
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Submitted on August 23, 2004
From the Physiologisches Institut (C.d.W.), Universität Lübeck, Germany; Physiologisches Institut (M.K., D.S., U.P.), Ludwig-Maximilians-Universität München, Germany; and Institut für Pharmakologie und Toxikologie (R.F., S.F., F.H.), Technische Universität München. * To whom correspondence should be addressed. E-mail: dewit{at}physio.uni-luebeck.de.
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 (
Revised on September 7, 2004
cGMP-Dependent Protein Kinase Mediates NO- but not Acetylcholine-Induced Dilations in Resistance Vessels In Vivo
Michael Koeppen;
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.
Key words: nitric oxide • endothelium • microcirculation
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