Effects of connexin-mimetic peptides on perfusion pressure in response to phenylephrine in isolated, perfused rat kidneys

Background Gap junction intercellular communication plays a fundamental role in various tissues and organs. Gap junctions transfer ions and molecules between adjacent cells and are formed by connexins (Cx). It is supposed that vascular conducted responses, which most likely spread through gap junctions in vascular beds, regulate microcirculatory blood flow and maintain vascular resistance. This study provides functional evidence supporting the critical role of gap junctions in a physiological setting and in phenylephrine (PE)-induced vasoconstriction using an ex vivo kidney perfusion technique. Methods Using the isolated, perfused kidney model, infusion of gap junction inhibitors and PE, we examined the local effect of gap junction communication. Additionally, gap junction proteins Cx37, Cx40 and Cx43 were detected by immunofluorescence. Results First, changes in the perfusion pressure were analyzed by infusing the nonselective gap junction uncoupler, 18a-glycyrrhetinic acid (18a-GA), and specific connexin-mimetic peptide inhibitors, 37,43Gap27, 40Gap27 and 43Gap26. Administration of 18a-GA and 43Gap26 significantly elevated perfusion pressure while infusion of 40Gap27 and 37,43Gap27 had no effect. Second, we examined the effect of infusing gap junction inhibitors on PEinduced vasoconstriction. Infusion of 18a-GA and 40Gap27 significantly suppressed the increase in perfusion pressure induced by PE, while 43Gap26 and 37,43Gap27 had no effect. Third, we confirmed by immunofluorescence that Cx37, Cx40 and Cx43 were found in the endothelial cells of interstitial microvessels and that Cx40 was localized in glomerular mesangial cells as well as in smooth muscle cells of the juxtaglomerular area. Conclusions This study showed that Cx43 plays a pivotal role in regulating renal vascular resistance and that Cx40 attenuates PE-induced vasoconstriction. These results provide new evidence that gap junctions may control renal circulation and vascular responses