renal autoregulation

Topics: Kidney, Renal physiology, Nephron Pages: 27 (1690 words) Published: October 30, 2014
Renal autoregulation: new perspectives
regarding the protective and regulatory
roles of the underlying mechanisms
Rodger Loutzenhiser,1 Karen Griffin,2
Geoffrey Williamson,3 and Anil Bidani2
1Smooth Muscle Research Group, University of
Calgary, Alberta, Canada; 2Department of
Internal Medicine, Loyola University Medical
Center and Edward Hines, Jr. Veterans Affairs
Hospital, Maywood, Illinois; and 3Department of
Electrical and Computer Engineering, Illinois
Institute of Technology, Chicago, Illinois

ABSTRACT
When the kidney is subjected to acute increases in blood
pressure (BP), renal blood flow (RBF) and glomerular filtration rate (GFR) are observed to remain relatively constant. Two
mechanisms, tubuloglomerular feedback (TGF) and the
myogenic response, are thought to act in concert to achieve a precise moment-by-moment regulation of GFR and distal salt
delivery. The current view is that this mechanism insulates
renal excretory function from fluctuations in BP. Indeed, the concept that renal autoregulation is necessary for normal renal function and volume homeostasis has long been a cornerstone
of renal physiology.

This article presents a very different view, at least
regarding the myogenic component of this response. We
suggest that its primary purpose is to protect the kidney against the damaging effects of hypertension. The arguments
advanced take into consideration the unique properties of the afferent arteriolar myogenic response that allow it to protect against the oscillating systolic pressure and the accruing
evidence that when this response is impaired, the primary
consequence is not a disturbed volume homeostasis but rather an increased susceptibility to hypertensive injury. It is
suggested that redundant and compensatory mechanisms
achieve volume regulation, despite considerable fluctuations in distal delivery, and the assumed moment-by-moment regulation of renal hemodynamics is questioned.

Evidence is presented suggesting that additional
mechanisms exist to maintain ambient levels of RBF and GFR
within normal range, despite chronic alterations in BP and
severely impaired acute responses to pressure. Finally, the
implications of this new perspective on the divergent roles of the myogenic response to pressure vs. the TGF response to
changes in distal delivery are considered, and it is proposed that
in
addition
to
TGF-induced
vasoconstriction,
vasodepressor responses to reduced distal delivery may play a critical role in modulating afferent arteriolar reactivity to integrate the regulatory and protective functions of the renal microvasculature, renal microcirculation; afferent arteriole; myogenic; tubuloglomerular feedback.

ONE OF THE MOST STRIKING CHARACTERISTICS of
the renal circulation is the ability of the kidney to maintain a constant renal blood flow (RBF) and glomerular filtration rate (GFR) as renal perfusion pressure is altered. The dual
regulation of both RBF and GFR is achieved by proportionate
changes in the preglomerular resistance and is believed to be mediated by two mechanisms, tubuloglomerular feedback
(TGF) and the renal myogenic response. TGF involves a flowdependent signal that is sensed at the macula densa and alters tone in the adjacent segment of the afferent arteriole via a mechanism that remains controversial but likely involves

adenosine and/or ATP.

The myogenic response involves a direct vasoconstriction of the afferent arteriole when this vessel is presented with an increase in transmural pressure. The current view is that these two mechanisms act in concert and that their primary role is to stabilize renal function by preventing pressure-induced fluctuations in RBF, GFR, and the delivery of filtrate to the distal tubule (distal delivery). Over the last two decades, evidence has accrued to indicate that this autoregulatory response plays a concurrent role in protecting the kidney from hypertensive injury. This view is based on...
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