Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles.
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 mum 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.
Sorensen
Charlotte Mehlin
CM
Univ. of Copenhagen, Dept. of Biomedical Sciences, The Panum Institute, Bldg. 10.5, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. cmehlin@mfi.ku.dk
Salomonsson
Max
M
Braunstein
Thomas Hartig
TH
Nielsen
Morten Schak
MS
Holstein-Rathlou
Niels-Henrik
NH
D000818:Animals; D001011:Aorta / Q000166:cytology; D001160:Arterioles / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000494:pharmacology; D017630:Connexins / Q000235:genetics / Q000494:pharmacology*; D004558:Electric Stimulation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply*; D018716:Molecular Mimicry; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D002118:Calcium; D018031:Connexin 43; D017630:Connexins; D010455:Peptides; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C082920:connexin 45