Glomerular feedback

Nonpeptide receptors Adenosine Aj Human cDNA Cardiac arrhythmia, asthma, myocardial ischemia, obesity, pain, renal disease, sleep apnea, stroke, cancer, inflammation, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Bradycardia, lipolysis inhibition, reduction of glomerular filtration and natriuresis, tubero-glomerular feedback, antinociception, renal vasodilatation-constriction, reduction of central cholinergic and noradrenergic nerve activity, presynaptic inhibition of excitatory neuro transmission... 

The steady-state component of the glomerular feedback is described by a sigmoidal relation between the muscular activation xjr of the afferent arteriole and the delayed version xj, of the Henle flow ... 

P.P. Leyssac and N.-H. Holstein-Rathlou, Tubulo-Glomerular Feedback Response Enhancement in Adult Spontaneously Hypertensive Rats and Effects of Anaesthetics, Pfltigers Archiv 413, 267-272 (1989). 

Tucker BJ, Steiner RW, Gushwa LC, Blantz RC. Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide. J Clin Invest 1978 62 993-1004. 

Increased delivery of salt to the TAL leads to activation of the macula densa and a reduction in glomerular filtration rate (GFR) by tubuloglomerular (TG) feedback. The mechanism of this feedback is secretion of adenosine by macula densa cells, which locally causes afferent arteriolar vasoconstriction. This vasoconstriction reduces GFR. Tubuloglomerular feedback-mediated reduction in GFR exacerbates the reduction that was initially caused by decreased cardiac output. Recent work with adenosine receptor antagonists (eg, rolofylline) has shown that it will soon be possible to circumvent this complication of diuretic therapy in heart failure patients. Using rolofylline with a diuretic will make it possible to produce an effective diuresis in patients with heart failure without causing renal decompensation. 

The TGF mechanism produces a negative feedback control on the rate of glomerular filtration. However, experiments performed on rats by Leyssac and Baumback [2] and by Leyssac and Holstein-Rathlou [3] in the 1980s demonstrated that the feedback regulation tends to be unstable and to generate large amplitude self-sustained oscillations in the proximal intratubular pressure with a period of 30-40 s. With different amplitudes and phases, similar oscillations have subsequently been observed in the distal intratubular pressure and in the chloride concentration near the terminal part of the loop of Henle [4],... 

Here, max and jrm n denote, respectively, the maximum and the minimum values of the muscular activation, a determines the slope of the feedback curve, S is the displacement of the curve along the flow axis, and Fneno is a normalization value for the Henle flow. The relation between the glomerular filtration and the flow into the loop of Henle can be obtained from open-loop experiments in which a paraffin block is inserted into the proximal tubule and the rate of glomerular filtration (or, alternatively, the so-called tubular stop pressure at which the filtration ceases) is measured as a function of an externally forced rate of flow of artificial tubular fluid into the loop of Henle. Translation of the experimental results into a relation between muscular activation and Henle flow is performed by means of the model, i.e., the relation is adjusted such that it can reproduce the experimentally observed steady state relation. We have previously discussed the significance of the feedback gain a in controlling the dynamics of the system, a is one of the parameters that differ between hypertensive and normotensive rats, and a will also be one of the control parameters in our analysis of the simulation results. 

Complex factors maintain constancy of renal blood flow and glomerular filtration despite widely varying arterial pressures. Such factors such as the renal nervous system, prostaglandins, angiotensin 11, adenosine, tubuloglomerular feedback as well as other factors... 

Wright FS, Schnermann J. Interference with feedback control of glomerular filtration rate by furosemide, triflocin, and cyanide. JClin Invest 1974 53 1695-708. 

Abbreviations renal blood flow (RBE), renal plasma flow (RPE), glomerular filtration rate (GFR), single nephron glomerular filtration rate (SNGFR), tubuloglomerular feedback (TGF). 

Acetazolamide, and probably other diuretics which inhibit carbonic anhydrase, cause a strong inhibition of proximal NaHCOg reabsorption and lithium reabsorption. However, unlike loop diuretics, acetazolamide does not interfere with tubuloglomerular feedback and causes a 20% decrease in glomerular filtration rate. The increase in absolute lithium excretion is somewhat lower than that caused by loop diuretics [22]. Colussi et al. [25] reported the effect of furosemide and acefazola-mide to be additive, indicating a dual site of action (i.e., inhibition of lithium reabsorption in both the proximal tubule and the loop of Henle). 

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