Analysis of energy metabolism and mechanism of loop diuretics in the thick ascending limb of Henle's loop in dog kidneys

Kiil, Fredrik; Sejersted, Ole M.

doi:10.1046/j.1365-201x.2003.01058.x

Cited by 6 publications

(5 citation statements)

References 33 publications

(69 reference statements)

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“…4. The V te values we predict under in vivo conditions are generally higher than in vitro estimates, which range between 3 and 10 mV (21,37), but are similar to other modeling predictions (44).…”

Section: Energy Efficiency Of Mtal Cellssupporting

confidence: 74%

Effects of pH and medullary blood flow on oxygen transport and sodium reabsorption in the rat outer medulla

Chen

Edwards

Layton

2010

American Journal of Physiology-Renal Physiology

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We used a mathematical model of O(2) transport and the urine concentrating mechanism of the outer medulla of the rat kidney to study the effects of blood pH and medullary blood flow on O(2) availability and Na(+) reabsorption. The model predicts that in vivo paracellular Na(+) fluxes across medullary thick ascending limbs (mTALs) are small relative to transcellular Na(+) fluxes and that paracellular fluxes favor Na(+) reabsorption from the lumen along most of the mTAL segments. In addition, model results suggest that blood pH has a significant impact on O(2) transport and Na(+) reabsorption owing to the Bohr effect, according to which a lower pH reduces the binding affinity of hemoglobin for O(2). Thus our model predicts that the presumed greater acidity of blood in the interbundle regions, where mTALs are located, relative to that in the vascular bundles, facilitates the delivery of O(2) to support the high metabolic requirements of the mTALs and raises the concentrating capability of the outer medulla. Model results also suggest that increases in vascular and tubular flow rates result in disproportional, smaller increases in active O(2) consumption and mTAL active Na(+) transport, despite the higher delivery of O(2) and Na(+). That is, at a sufficiently high medullary O(2) supply, O(2) demand in the outer medulla does not adjust precisely to changes in O(2) delivery.

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Section: Energy Efficiency Of Mtal Cellssupporting

confidence: 74%

Effects of pH and medullary blood flow on oxygen transport and sodium reabsorption in the rat outer medulla

Chen

Edwards

Layton

2010

American Journal of Physiology-Renal Physiology

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“…56 In addition, oxygen consumption is very high in the outer medulla because of the high levels of active ion transport in the thick ascending limbs of the loops of Henle (TALs) and proximal straight tubules, thereby reducing the oxygen content even further in this region. [56][57][58][59][60][61] In contrast, oxygen consumption is very small in the inner medulla because there is no active transport by the thin loop of Henle and therefore tissue oxygen tension is well preserved. 56 Thus, the outer medulla is the anatomical site most susceptible to injuries such as ischemia.…”

Section: Albuminuria and Endothelial Dysfunctionmentioning

confidence: 99%

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

et al. 2009

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Albuminuria is closely associated with stroke and cardiovascular diseases (CVDs) as well as the salt sensitivity of blood pressure (BP). Although albuminuria may reflect generalized endothelial dysfunction, there may be more specific hemodynamic mechanisms underlying these associations. Cerebral hemorrhage and infarction occur most frequently in the area of small perforating arteries that are exposed to high pressure and that have to maintain strong vascular tone in order to provide large pressure gradients from the parent vessels to the capillaries. Analogous to the perforating arteries are the glomerular afferent arterioles of the juxtamedullary nephrons. Hypertensive vascular damage occurs first and more severely in the juxtamedullary glomeruli. Therefore, albuminuria may be an early sign of vascular damages imposed on 'strain vessels' such as perforating arteries and juxtamedullary afferent arterioles. Coronary circulation also occurs under unique hemodynamic conditions, in which the entire epicardial segments are exposed to very high pressure with little flow during systolic phases. From the evolutionary point of view, we speculate that such circulatory systems in the vital organs are mandatory for survival under the danger of hypoperfusion due to difficult access to salt and water as well as high risks of wound injuries. In addition, albuminuria would indicate an impairment of renal medullary circulation, downstream from the juxtamedullary glomeruli, and therefore an impaired pressure natriuresis, which would lead to salt sensitivity of BP. Our 'strain vessel hypothesis' may explain why hypertension and diabetes, unforeseen in the concept of evolution, preferentially affect vital organs such as the brain, heart and kidney.

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“…THE KIDNEY CONSUMES oxygen, mainly to generate potential energy for tubular reabsorption (6,20,32,41). The renal blood flow (RBF) is normally high relative to the kidney's demand for oxygen, so the kidney extracts only a small fraction of the oxygen that is supplied to it.…”

mentioning

confidence: 99%

“…Changes in Q O 2 /T Na might occur for multiple reasons. For example, shifting the burden of reabsorption from the proximal tubule to the loop of Henle increases the average cost of reabsorbing a sodium ion (20,22). Theoretically, the efficiency of reabsorption might also be altered within a single nephron segment by changing the permeability of intercellular tight junctions, changing the number of ATP molecules formed per oxygen molecule consumed in mitochondria, or by switching to a different transport mechanism.…”

mentioning

confidence: 99%

Kidney oxygen consumption, carbonic anhydrase, and proton secretion

Deng¹,

Miracle²,

Lortie³

et al. 2006

American Journal of Physiology-Renal Physiology

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Oxygen consumed by the kidney (Q(O(2))) is primarily obligated to sodium reabsorption (T(Na)). The relationship of Q(O(2)) to T(Na) (Q(O(2))/T(Na)) may be altered by hormones and autacoids. To examine whether Q(O(2))/T(Na) depends on the mechanism of sodium reabsorption, we first evaluated the effects on Q(O(2)) and Q(O(2))/T(Na) of benzolamide (BNZ), a proximal diuretic that works by inhibiting membrane carbonic anhydrase. During BNZ infusion in anesthetized rats, Q(O(2)) increased by 50% despite a 25% decline in T(Na). However, BNZ failed to increase Q(O(2))/T(Na) when given along with the adenosine A1 receptor blocker, DPCPX, which inhibits basolateral Na-bicarbonate cotransport (NBC1), or EIPA, which inhibits sodium-hydrogen exchange (NHE). Incubating freshly harvested rat proximal tubules with BNZ also caused Q(O(2))to increase by 62%, an effect that was prevented by blocking the apical NHE3 with S3226. Blocking NBC1 or NHE3 in the proximal tubule will have opposite effects on cell pH, but both maneuvers should reduce active chloride transport. In conclusion, inhibiting membrane carbonic anhydrase in the proximal tubule increases Q(O(2)) and reduces the energy efficiency of sodium reabsorption by the kidney. This is not purely due to shifting the burden of reabsorption to a more expensive site downstream from the proximal tubule. Instead, increased cost may be incurred within the proximal tubule as the result of increased active chloride transport.

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Analysis of energy metabolism and mechanism of loop diuretics in the thick ascending limb of Henle's loop in dog kidneys

Cited by 6 publications

References 33 publications

Effects of pH and medullary blood flow on oxygen transport and sodium reabsorption in the rat outer medulla

Effects of pH and medullary blood flow on oxygen transport and sodium reabsorption in the rat outer medulla

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

Kidney oxygen consumption, carbonic anhydrase, and proton secretion

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