Autoregulation of filtration rate in the absence of macula densa-glomerulus feedback

Maddox, DA; Troy, JL; Brenner, B M

doi:10.1152/ajplegacy.1974.227.1.123

Cited by 22 publications

(7 citation statements)

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“…The values we found for snGFR at both proximal and distal sites, 30 ± 1 and 33 ± 2 nl/min, respectively, are close to this mean. The fact that we found no difference between the filtration rates at proximal and distal sites despite very large sample sizes, 76 and 90, respectively, supports the view that tubulo-glomerular feddback does not exist or must be nonoperative in normal nondiuretic rats [19,22], As mentioned above, many have proposed that the renin-angiotensin system mediates the changes in arteriolar resistance that occur during renal autoregulatory phenomena. Autoregulation occurs over a range of blood pressures, both below and above normal [18].…”

Section: Discussionsupporting

confidence: 78%

Tubulo-Glomerular Feedback in the Rat

Churchill

McDonald

1977

Nephron

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Using conventional micropuncture techniques in 53 adult Sprague-Dawley rats anesthetized with sodium pentobarbital, single nephron GFR at proximal sites (snGFR_prox) averaged 30 ± 1 nl/min (76 tubules) and at distal sites (snGFR_diS), 33 ± 2 nl/min (90 tubules). Thus, in spite of interruption of macula densa fluid flow during its measurement, snGFR_proX was not significantly greater than snGFR_diS (p > 0.05). Whole kidney GFR averaged 0.9 ± 0.07 ml/min before and 1.0 ± 0.05 ml/min during an intravenous infusion of SQ20,881, a substance which inhibits production of angiotensin II. Similarly, snGFR_diS was unaffected by SQ20,881; the mean difference between paired snGFRdis (collection during NaCl infusion minus recollection at same sites during SQ20,881 infusion) was 6 ± 4 nl/min (p > 0.5). These results suggest that under the conditions of the experiments, tubulo-glomerular feedback is not operative and that angiotensin II plays no role in controlling filtration.

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Section: Discussionsupporting

confidence: 78%

Tubulo-Glomerular Feedback in the Rat

Churchill

McDonald

1977

Nephron

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“…Another thought is that MD-TGF is essentially normal shortly after UNx despite the increase in SNGFR (117, 1372). Efficient GFR autoregulation persisted in volume-expanded UNx rats in the absence of a demonstrable MD-TGF, implicating a strong myogenic response accounting for complete autoregulation (945). One week of administration of an AT 1 receptor blocker attenuated the MD-TGF activity in shamoperated rats, but paradoxically normalized the previously nonexistent MD-TGF response in 5/6 Nx rats (1372).…”

Section: Carlström Et Almentioning

confidence: 92%

Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

378

383

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Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca(2+)]i occurs predominantly by Ca(2+) influx through L-type voltage-operated Ca(2+) channels (VOCC). Increased [Ca(2+)]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca(2+) from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca(2+) sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

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“…The evidence for the theory of autoregulation of fIltration rate by means of macula densa glomerulus feedback remains controversial (Schnermann et al, 1973;Thurau, 1973;Maddox et al, 1974).…”

Section: Reabsorption By the Collecting Ductmentioning

confidence: 99%

Diuretics

Davies

Wilson

1975

Drugs

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Despite the bewildering number of diuretics available to the physician, these drugs can be divided into 4 main groups, characterised by their site of action on sodium reabsorption in the kidney. Drugs acting on the ascending limb of the loop of Henle have a powerful but short acting diuretic effect; they include frusemide, ethacrynic acid and bumetanide. The benzothiadiazines and related compounds have a moderate diuretic action spread over a longer period, whilst the potassium-sparing diuretics, triamterene, amiloride and spironolactone, have only a weak diuretic effect but a marked ability to diminish urinary potassium excretion. The fourth group is made up of miscellaneous substances which function as vasodilator or osmotic agents. The pathogenesis of oedema formation in heart failure is outlined and a logical approach to treatment suggested. Duiretics are being increasingly used in the treatment of non-oedematous states, in particular hypertension, diabetes insipidus and hypercalciuria; their exact role in pregnancy and acute renal failure remains controversial. Side-effects can be related to their effect on electrolyte excretion and include hypokalaemia, hyponatraemia, hyperkalaemia and hyperuricaemia. The incidence of disturbed carbohydrate tolerance in previously normal individuals is low. Other less common side-effects are also discussed.

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Autoregulation of filtration rate in the absence of macula densa-glomerulus feedback

Cited by 22 publications

References 0 publications

Tubulo-Glomerular Feedback in the Rat

Tubulo-Glomerular Feedback in the Rat

Renal Autoregulation in Health and Disease

Diuretics

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