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Influence of connexin45 on renal autoregulation.

Authors
  • Møller, Sophie1
  • Jacobsen, Jens Christian Brings1
  • Braunstein, Thomas H2
  • Holstein-Rathlou, Niels-Henrik1
  • Sorensen, Charlotte M1
  • 1 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 2 Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
Type
Published Article
Journal
AJP Renal Physiology
Publisher
American Physiological Society
Publication Date
Mar 01, 2020
Volume
318
Issue
3
Identifiers
DOI: 10.1152/ajprenal.00185.2019
PMID: 31984796
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Renal autoregulation is mediated by the myogenic response and tubuloglomerular feedback (TGF) working in concert to maintain renal blood flow and glomerular filtration rate despite fluctuations in renal perfusion pressure. Intercellular communication through gap junctions may play a role in renal autoregulation. We examine if one of the building blocks in gap junctions, connexin45 (Cx45), which is expressed in vascular smooth muscle cells, has an influence on renal autoregulatory efficiency. The isolated perfused juxtamedullary nephron preparation was used to measure afferent arteriolar diameter changes in response to acute changes in renal perfusion pressure. In segmental arteries, pressure myography was used to study diameter changes in response to pressure changes. Wire myography was used to study vasoconstrictor and vasodilator responses. A mathematical model of the vascular wall was applied to interpret experimental data. We found a significant reduction in the afferent arteriolar constriction in response to acute pressure increases in Cx45 knockout (KO) mice compared with wild-type (WT) mice. Abolition of TGF caused a parallel upward shift in the autoregulation curve of WT animals but had no effect in KO animals, which is compatible with TGF providing a basal tonic contribution in afferent arterioles whereas Cx45 KO animals were functionally papillectomized. Analysis showed a shift toward lower stress sensitivity in afferent arterioles from Cx45 KO animals, indicating that the absence of Cx45 may also affect myogenic properties. Finally, loss of Cx45 in vascular smooth muscle cells appeared to associate with a change in both structure and passive properties of the vascular wall.

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