Renal autoregulation in P2X1 knockout mice

Academic Article

Abstract

  • Autoregulation of renal blood flow is an established physiological phenomenon, however the signalling mechanisms involved remain elusive. Autoregulatory adjustments in preglomerular resistance involve myogenic and tubuloglomerular feedback (TGF) influences. While there is general agreement on the participation of these two regulatory pathways, the signalling molecules and effector mechanisms have not been identified. Currently, there are two major hypotheses being considered to explain the mechanism by which TGF signals are transmitted from the macula densa to the afferent arteriole. The adenosine hypothesis proposes that the released adenosine triphosphate (ATP) is hydrolysed to adenosine and this product stimulates preglomerular vasoconstriction by activation of A1 receptors on the afferent arteriole. Alternatively, the P2 receptor hypothesis postulates that ATP released from the macula densa directly stimulates afferent arteriolar vasoconstriction by activation of ATP-sensitive P2X1 receptors. This hypothesis has emerged from the realization that P2X1 receptors are heavily expressed along the preglomerular vasculature. Inactivation of P2X1 receptors impairs autoregulatory responses while afferent arteriolar responses to A1 adenosine receptor activation are retained. Autoregulatory behaviour is markedly attenuated in mice lacking P2X1 receptors but responses to adenosine A1 receptor activation remain intact. More recent experiments suggest that P2X1 receptors play an essential role in TGF-dependent vasoconstriction of the afferent arteriole. Interruption of TGF-dependent influences on afferent arteriolar diameter, by papillectomy or furosemide treatment, significantly attenuated pressure-mediated afferent arteriolar vasoconstriction in wildtype mice but had no effect on the response in P2X 1 knockout mice. Collectively, these observations support an essential role for P2X1 receptors in TGF-mediated afferent arteriolar vasoconstriction.
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    Digital Object Identifier (doi)

    Author List

  • Inscho EW; Cook AK; Imig JD; Vial C; Evans RJ
  • Start Page

  • 445
  • End Page

  • 453
  • Volume

  • 181
  • Issue

  • 4