Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Abstract

dani. Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 290: R1153-R1167, 2006. doi:10.1152/ajpregu.00402.2005.-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 flow-dependent 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 (30,80,144). The myo...

Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction

“…However, this approach is not clinically feasible. The absence of GFR changes despite systemic blood pressure increase in the present study may be due to activation of renal autoregulation modulating afferent arteriolar tone by a combination of tubuloglomerular feedback and myogenic effects (27). The complex autoregulatory mechanisms may to some extent be influenced by ANG II and NO as suggested in the studies from the normal adult rat kidney (18).…”

Cerebrovascular Damage in Late-Life Depression Is Associated With Structural and Functional Abnormalities of Subcutaneous Small Arteries

“…20,29 In patients with type 2 diabetes mellitus, a dual process of loss of autoregulation and hypertrophic remodeling has been proposed as a contributory factor in the development of target organ damage. 30,31 Clearly, the small arteries studied were from a different circulation from those that may be involved in the pathogenesis of vascular depression, which are presumably small penetrating pial arteries. As such, the findings are associative, but it should be noted that the structural and functional changes that occur in human subcutaneous small arteries in response to hypertension and diabetes mellitus 20 are mirrored in mesenteric, 32 coronary, 33 and cerebral 15 arteries.…”

ATP as a mediator of macula densa cell signalling

“…This change in the luminal environment would be sensed by the macula densa and signals sent to the afferent arteriole, resulting in vasoconstriction and decreases in GFR and renal blood flow back to normal. There is certainly a component of autoregulation that is also due to myogenic behaviour of the smooth muscle cells; the current discussions in this area of research deal with the relative contributions of TGF and myogenic activity to autoregulation [94]. The contribution of both systems to autoregulation may not be fixed, but could vary due to changes in physiological conditions or disease processes.…”