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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/R840    most recent 00491.2007v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sorensen, C. M. Articles by Holstein-Rathlou, N.-H. Search for Related Content PubMed PubMed Citation Articles by Sorensen, C. M. Articles by Holstein-Rathlou, N.-H.

HEMODYNAMICS AND CARDIORENAL INTEGRATION

Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles

¹Department of Biomedical Sciences, Division of Renal and Cardiovascular Research, The Panum Institute and ²The Danish National Research Foundation Centre for Cardiac Arrhythmia Research, University of Copenhagen, Copenhagen North, Denmark

Submitted 7 July 2007 ; accepted in final form 1 July 2008

Vascular conducted responses are believed to play a central role in controlling the microcirculatory blood flow. The responses most likely spread through gap junctions in the vascular wall. At present, four different connexins (Cx) have been detected in the renal vasculature, but their role in transmission of conducted vasoconstrictor signals in the preglomerular arterioles is unknown. Connexin mimetic peptides were previously reported to target and inhibit specific connexins. We, therefore, investigated whether conducted vasoconstriction in isolated renal arterioles could be blocked by the use of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response was measured 500 µm from the site of stimulation. Application of connexin mimetic peptides directed against Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit the propagated response, whereas the nonselective gap junction uncoupler carbenoxolone completely abolished the propagated response. However, the connexin mimetic peptides were able to reduce dye coupling between rat aorta endothelial cells shown to express primarily Cx40. In conclusion, we did not observe any attenuating effects on conducted calcium responses in isolated rat interlobular arteries when exposed to connexin mimetic peptides directed against Cx40, 37/43, or 45. Further studies are needed to determine whether conducted vasoconstriction is mediated via previously undescribed pathways.

vasoconstriction; conducted responses; intercellular communication