Sophie Møller, Jens Christian Brings Jacobsen, Thomas Hartig Braunstein, Niels-Henrik Holstein-Rathlou, Charlotte M Sorensen
2020 AJP - Renal Physiology  
Renal autoregulation is mediated by the myogenic response and the 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, connexin 45 (Cx45), which is expressed in vascular smooth muscle cells (VSMCs), has an influence on renal autoregulatory
more » ... fficiency. 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) compared to wildtype (WT) mice. Abolition of TGF caused a parallel upward shift in the autoregulation curve of the WT animals but had no effect in the KO group, compatible with the TGF providing a basal tonic contribution in afferent arterioles whereas Cx45 KO animals were functionally papillectomized. Analysis showed a shift towards lower stress sensitivity in afferent arterioles from Cx45 KO animals indicating that absence of Cx45 may also affect myogenic properties. Finally, loss of Cx45 in VSMCs appeared to associate with a change in both structure and passive properties of the vascular wall.
doi:10.1152/ajprenal.00185.2019 pmid:31984796 fatcat:grmby7qymfc6hm76rfej2aeqfa