Tubuloglomerular feedback in Dahl rats

Karlsen, Finn Michael; Leyssac, P. P.; Holstein‐Rathlou, Niels‐Henrik

doi:10.1152/ajpregu.1998.274.6.r1561

Cited by 19 publications

(20 citation statements)

References 26 publications

(44 reference statements)

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“…[25][26][27] It has also been shown that the myogenic responsiveness in DS rats is diminished. 28 Karlsen et al 29 reported that tubuloglomerular feedback responsiveness in hypertensive DS rats remained intact, which was not attenuated, as might be expected with reductions of intrarenal Ang II levels. Thus, these pathophysiological characteristics of intrarenal function in DS rats are consistent with an inappropriately enhanced AGT in the kidney, which may contribute to the development and maintenance of hypertension.…”

Section: Kobori Et Al Angiotensinogen In Dahl Rats 595mentioning

confidence: 83%

Enhancement of Intrarenal Angiotensinogen in Dahl Salt-Sensitive Rats on High Salt Diet

et al. 2003

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Abstract-This study was performed to examine whether there is an inappropriate regulation of intrarenal angiotensinogen in Dahl-salt sensitive rats (DS) fed a high salt diet (HS). Dahl salt-resistant rats (DR) and DS were maintained on HS (8% NaCl) or low salt diet (LS, 0.3% NaCl) for 4 weeks. Systolic blood pressure (SBP), measured by tail-cuff plethysmography, was unaltered in DR (DRϩHS, 127Ϯ3 mm Hg, nϭ5; DRϩLS, 126Ϯ3, nϭ5); however, SBP was significantly increased in DSϩHS (208Ϯ7, nϭ9) compared with DSϩLS (134Ϯ2, nϭ5 Key Words: angiotensin II Ⅲ angiotensinogen Ⅲ rats, Dahl Ⅲ kidney Ⅲ urine Ⅲ hypertension, sodium-dependent Ⅲ Western blot V arious epidemiological studies have showed a correlation of dietary salt intake with the prevalence and progression of hypertension. 1 Although the degree of salt sensitivity is variable, some individuals are particularly prone to have hypertension in response to an increased dietary salt intake. Subjects with essential hypertension have a higher frequency of salt sensitivity than is found in the normotensive population. 2 There is some evidence that salt sensitivity is associated with low plasma renin activity (PRA) and impaired renal sodium excretion. However, the mechanisms underlying this phenomenon are poorly understood. 3 Dahl salt-sensitive (DS) rats have been used as a model of human salt-sensitive hypertension because salt loading exaggerates the development of hypertension in strains that are genetically predisposed to hypertension. 4 Mature DS rats are reported to have low PRA levels, which has been interpreted as being indicative of an overall suppression of the renin-angiotensin system (RAS) 4 ; however, few studies of angiotensinogen (AGT) have been carried out in these rats. Although generally considered to be characterized by a low activity of circulating RAS, recent studies indicate that treatment with angiotensin (Ang) I-converting enzyme inhibitors or Ang II type I receptor antagonists reduces cardiac and/or renal dysfunction in DS rat fed a high salt diet (HS). [5][6][7][8][9][10] These findings suggest that the local RAS may be inappropriately activated and contribute to the development of hypertension in this animal model.Previous studies have demonstrated that Ang II infusions to normal rats result in paradoxical increases in renal expression of AGT mRNA 11,12 and protein. 13 Furthermore, urinary excretion of AGT was significantly increased in Ang II-infused rats, which was associated with an enhancement of intrarenal Ang II levels. 14 These results indicate that intrarenal AGT levels are not necessarily associated with increased plasma or renal renin levels. However, the extent to which this may occur in DS rats has not been determined. Therefore, this study was performed to determine if there is an inappropriate regulation of intrarenal AGT in DS rats fed HS and if enhanced

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Section: Kobori Et Al Angiotensinogen In Dahl Rats 595mentioning

confidence: 83%

Enhancement of Intrarenal Angiotensinogen in Dahl Salt-Sensitive Rats on High Salt Diet

et al. 2003

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“…Indeed, dynamic autoregulation studies in the conscious 5/6 ablation model suggest an attenuation of the myogenic component (18). Moreover, in the Fawn-Hooded rat, the Dahl salt-sensitive rat, and the BNR, the genetic defect in autoregulation seems to primarily involve the myogenic mechanism, while TGF is intact or even enhanced (87,88,145). In this context, an examination of the susceptibility to hypertensive injury in the gene deletion models with absent or impaired TGF (30,80,135,144) would be illuminating.…”

Section: Consequences Of Impaired Renal Autoregulation On Renal Protementioning

confidence: 99%

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

Loutzenhiser

Griffin²,

Bidani³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

233

244

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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...

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“…The efficacy of model TGF regulation can be quantified by calculating feedback compensation, an index used in experimental investigations (10,20,26). Feedback compensation is defined by (10) where M, the magnification, is defined by…”

Section: Mathematical Modelmentioning

confidence: 99%

Effect of sustained flow perturbations on stability and compensation of tubuloglomerular feedback

Oldson

Moore²,

Layton³

2003

American Journal of Physiology-Renal Physiology

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mathematical model previously formulated by us predicts that limit-cycle oscillations (LCO) in nephron flow are mediated by tubuloglomerular feedback (TGF) and that the LCO arise from a bifurcation that depends heavily on the feedback gain magnitude, ␥, and on its relationship to a theoretically determined critical value of gain, ␥ c. In this study, we used that model to show how sustained perturbations in proximal tubule flow, a common experimental maneuver, can initiate or terminate LCO by changing the values of ␥ and ␥c, thus changing the sign of ␥ Ϫ ␥ c. This result may help explain experiments in which intratubular pressure oscillations were initiated by the sustained introduction or removal of fluid from the proximal tubule (Leyssac PP and Baumbach L. Acta Physiol Scand 117: 415-419, 1983). In addition, our model predicts that, for a range of TGF sensitivities, sustained perturbations that initiate or terminate LCO can yield substantial and abrupt changes in both distal NaCl delivery and NaCl delivery compensation, changes that may play an important role in the response to physiological challenge. kidney; renal hemodynamics; autoregulation; mathematical model; nonlinear dynamics THE TUBULOGLOMERULAR FEEDBACK (TGF) SYSTEM is a key moment-to-moment regulator of the single-nephron glomerular filtration rate (SNGFR). A large body of experimental and theoretical evidence indicates that TGF can mediate sustained, regular oscillations of 20-47 mHz in tubular flow, pressure, and intratubular thick ascending limb (TAL) NaCl concentration (4,6,7,12,18). These regular oscillations are called limit-cycle oscillations (LCO) because, after initiation, they tend to more and more closely approximate a fixed cycle, provided that system parameters do not change. Spontaneous LCO appear to occur in large numbers of nephrons, as they have been detected in recordings of renal blood flow and pressure taken in conscious, chronically instrumented dogs (8).A common and useful method of investigating TGF is to impose sustained perturbations of proximal tubule (PT) fluid flow in a freely flowing nephron where the TGF feedback loop is closed and functional (3,5,6,20,21,26). Using this technique, Leyssac and collaborators (5, 17, 18) have demonstrated that LCO can be initiated or extinguished in halothane-anesthetized rats by insertion or removal of PT fluid, findings that indicate that PT fluid flow can have a substantial effect on the stability of the TGF system. Some insight into the basis of this phenomenon is provided by our previous investigations of the TGF-mediated 22). These modeling studies indicate that LCO will emerge for sufficiently large feedback loop gain magnitude (12), that the parameter regime that supports LCO may overlap the parameter regime of normal TGF operation, that a gain magnitude near that needed for LCO will produce maximal feedback compensation (16), and that LCO may augment NaCl delivery to the distal nephron (16). A finding of fundamental importance is that the emergence of LCO depends on key TGF syst...

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Tubuloglomerular feedback in Dahl rats

Cited by 19 publications

References 26 publications

Enhancement of Intrarenal Angiotensinogen in Dahl Salt-Sensitive Rats on High Salt Diet

Enhancement of Intrarenal Angiotensinogen in Dahl Salt-Sensitive Rats on High Salt Diet

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

Effect of sustained flow perturbations on stability and compensation of tubuloglomerular feedback

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