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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/H2341    most recent 01061.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Rodenwaldt, B. Articles by de Wit, C. Search for Related Content PubMed PubMed Citation Articles by Rodenwaldt, B. Articles by de Wit, C.

Endogenous and exogenous NO attenuates conduction of vasoconstrictions along arterioles in the microcirculation

¹Institut für Physiologie, Universität Lübeck, 23538 Lübeck; and ²Physiologisches Institut, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany

Submitted 27 September 2006 ; accepted in final form 7 January 2007

Vascular coordination in the microcirculation depends on gap junctional intercellular communication (GJIC), which is reflected by the conduction of locally initiated vasomotor responses. However, little is known about the regulation of GJIC in vivo. We hypothesized that endothelial NO regulates GJIC and therefore studied whether conduction of constrictions and dilations along the vessel wall is modulated by modifying the level of microcirculatory NO. Arterioles were focally stimulated using high K⁺ or acetylcholine in the cremaster muscle in situ, and diameter changes were assessed at the local and remote upstream sites by intravital microscopy. Local stimulation with K⁺ initiated a constriction that conducted along the arteriole with diminishing amplitude (length constant : 371 ± 42 µm). After N-nitro-L-arginine (L-NNA), increased to 507 ± 30 µm, indicating that GJIC is attenuated by endogenous NO. Exogenous NO, but not adenosine, reduced after L-NNA in a reversible, concentration-dependent, and mainly cGMP-dependent manner as assessed by inhibition of soluble guanylate cyclase. In endothelial NO synthase-deficient mice, was 530 ± 80 µm and thus similar to that in wild-type mice after L-NNA. Exogenous NO likewise reduced in these mice. The effects of NO were comparable to those of wild-type animals in Cx40-deficient mice, which excludes Cx40 as a specific target of NO. In contrast to constrictions, the amplitude of conducted dilations on acetylcholine did not diminish up to 1,300 µm and were not altered by L-NNA or exogenous NO. We conclude that endogenously released NO attenuates the conduction of vasoconstrictions most likely due to a modulation of gap junctional conductivity. We suggest that this effect is specific for smooth muscle cells, which probably transmit constricting signals, and involves connexins other than Cx40. This mechanism may support the dilatory potency of NO by preventing the conduction of remote vasoconstrictions into areas with basal or activated NO release.

conducted responses; gap junctional communication; connexins; nitric oxide