Renal autoregulation in P2X1 knockout mice

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 pa...

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Bibliographic Details
Published in:Acta physiologica Scandinavica 2004-08, Vol.181 (4), p.445-453
Main Authors: Inscho, E. W., Cook, A. K., Imig, J. D., Vial, C., Evans, R. J.
Format: Article
Language:English
Subjects:
A1 receptors
adenosine triphosphate
Adenosine Triphosphate - physiology
afferent arterioles
Animals
Arterioles - physiology
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Homeostasis - physiology
Mice
Mice, Knockout
NF279
P2X1 knockout mice
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - physiology
Receptors, Purinergic P2X
Renal Circulation - physiology
renal microcirculation
Transforming Growth Factors - physiology
tubuloglomerular feedback
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Online Access:Get full text
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Summary: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 wild‐type mice but had no effect on the response in P2X1 knockout mice. Collectively, these observations support an essential role for P2X1 receptors in TGF‐mediated afferent arteriolar vasoconstriction.
ISSN:0001-6772
1365-201X
DOI:10.1111/j.1365-201X.2004.01317.x