Influence of perfusate osmolality on stop-flow pressure feedback responses in the dog

Navar, L. G.; Bell, P. Darwin; Thomas, Callum; Ploth, David W.

doi:10.1152/ajprenal.1978.235.4.f352

Cited by 17 publications

(11 citation statements)

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“…There are no discernible differences in the efficacy of loop diuretics to inhibit NKCC2 as judged from comparable diuretic potencies of these agents across species. Furthermore, loop diuretics have been shown to cause inhibition of TGF in both dogs and rats (25,40). Thus it is highly unlikely that the different hemodynamic responses to furosemide in these species reflect a difference in diuretic-induced TGF inhibition and vasodilatation.…”

Section: Discussionmentioning

confidence: 99%

Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

Oppermann¹,

Hansen²,

Castrop³

et al. 2007

American Journal of Physiology-Renal Physiology

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Oppermann M, Hansen PB, Castrop H, Schnermann J. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice. Am J Physiol Renal Physiol 293: F279-F287, 2007. First published May 9, 2007; doi:10.1152/ajprenal.00073.2007.-Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or N G -nitro-Larginine methyl ester, furosemide caused a dose-dependent increase of vascular diameter, but it was without effect in vessels from NKCC1Ϫ/Ϫ mice suggesting that inhibition of NKCC1 mediates dilatation in afferent arterioles. In the intact kidney, however, furosemide (2 mg/kg iv) caused a 50.5 Ϯ 3% reduction of total renal blood flow (RBF) and a 27% reduction of superficial blood flow (SBF) accompanied by a marked and immediate increase of tubular pressure and volume. At 10 mg/kg, furosemide reduced RBF by 60.4 Ϯ 2%. Similarly, NKCC1Ϫ/Ϫ mice responded to furosemide with a 45.4% decrease of RBF and a 29% decrease of SBF. Decreases in RBF and SBF and increases of tubular pressure by furosemide were ameliorated by renal decapsulation. In addition, pretreatment with candesartan (2 mg/kg) or indomethacin (5 mg/kg) attenuated the reduction of RBF and peak urine flows caused by furosemide. Our data indicate that furosemide, despite its direct vasodilator potential in isolated afferent arterioles, causes a marked increase in flow resistance of the vascular bed of the intact mouse kidney. We suggest that generation of angiotensin II and/or a vasoconstrictor prostaglandin combined with compression of peritubular capillaries by the expanding tubular compartment are responsible for the reduction of RBF in vivo. renal blood flow; superficial blood flow; candesartan; decapsulation; tubular pressure; NKCC1 knockout LOOP DIURETICS LIKE FUROSEMIDE or bumetanide are widely used antihypertensive and diuretic drugs. Diuresis and loss of extracellular fluid result from an inhibitory interaction of the diuretics with the Na-K-2Cl cotransporter NKCC2, the major NaCl uptake pathway across the apical membrane of the thick ascending limb (TAL). In addition, loop diuretics also inhibit NKCC1, the second isoform of the Na-K-2Cl cotransporter that is more widely expressed than NKCC2 (11). In polarized cells, NKCC1 is typically located in the basolateral membrane, and NKCC1-mediated NaCl uptake therefore is an early step in transepithelial NaCl secretion. In nonpolarized cells, NKCC1 is believed to play a role in cell volume regulation and maintenance of membrane potential. NKCC1 is widely expressed in the vasculature, and inhibition of this transporter may account for direct vascular effects of loop diuretics that appear to be vasodilatory in most vascular beds (8). The interaction between the diuretics and the two different transporter isoforms occurs with similar a...

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Section: Discussionmentioning

confidence: 99%

Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

Oppermann¹,

Hansen²,

Castrop³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…Some experiments have indicated that tubular fluid osmolality may also regulate the nephron feedback response although this remains controversial (4,43). "Feedback inhibition" of SNGFR occurs during infusion of hypertonic NaCl but not hypertonic NaHCO3 (44), is augmented by prior dietary salt restriction (45), and is independent of the nervous system (46).…”

Section: Experimental Protocolmentioning

confidence: 99%

“…To define the separate effects of an acute increase in plasma sodium (PNa), chloride (Pci) or osmolality (Posmoi), changes in renal blood flow (RBF) and GFR were measured during intrarenal infusions of hypertonic NaCl, NaHCO3, Na acetate, dextrose, NH4Cl or NH4acetate to denervated kidneys. The infusions raised Posmol at the experimental kidney by [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] mosmol. RBF increased abruptly by 10-30% with all hypertonic infusions indicating that an acute increase in plasma tonicity causes renal vasodilatation.…”

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confidence: 99%

Regulation of Renal Blood Flow by Plasma Chloride

Wilcox¹

1983

J. Clin. Invest.

599

340

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A B S T R A C T Micropuncture studies have shown that glomerular filtration rate (GFR) falls in response to a rise in Na' or Cl-concentrations in the loop of Henle, whereas studies in isolated kidneys have shown that GFR falls in response to osmotic diuresis. To define the separate effects of an acute increase in plasma sodium (PNa), chloride (Pci) or osmolality (Posmoi), changes in renal blood flow (RBF) and GFR were measured during intrarenal infusions of hypertonic NaCl, NaHCO3, Na acetate, dextrose, NH4Cl or NH4acetate to denervated kidneys. The infusions raised Posmol at the experimental kidney by [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] mosmol. RBF increased abruptly by 10-30% with all hypertonic infusions indicating that an acute increase in plasma tonicity causes renal vasodilatation. Renal vasodilatation persisted or increased further during infusion of dextrose, NaHCO3 and Na acetate, but GFR was unchanged. In contrast, during infusion of the two Clcontaining solutions, vasodilatation was reversed after 1-5 min and RBF and GFR decreased (P < 0.01) below preinfusion levels. Prior salt depletion doubled the vasoconstriction seen with hypertonic NaCl infusions. Overall, changes in RBF were unrelated to changes in PNa or fractional Na or fluid reabsorption but correlated with changes in P(:I (r = -0.91) and fractional Cl-reabsorption (r = 0.94). The intrafemoral arterial infusion of the two Cl-containing solutions did not increase femoral vascular resistance. In conclusion, hyperchloremia produces a progressive renal vasoconstriction and fall in GFR that is independent of the renal nerves, is potentiated by prior salt depletion and is related to tubular Cl-reabsorption. Chloride-induced vasoconstriction appears specific for the renal the adequacy of the extracellular volume (ECV)' is threatened by salt depletion, impaired proximal tubule reabsorption or a high perfusion pressure, renal vasoconstriction restricts the volume of filtrate delivered to the tubules (1-5). A mechanism that can relate glomerular filtration to distal fluid delivery has been identified in micropuncture experiments in which single nephron glomerular filtration rate (SNGFR) has been found to fall during a selective increase in the Na+ or Cl-concentrations or osmolality of early distal tubule fluid (6-8).In previous experiments, we (9) and others (10, 11) showed that intrarenal infusion of hypertonic NaCI solution causes transient vasodilatation followed by sustained vasoconstriction. Schnermann et al. (8) demonstrated that retrograde injection of Cl-containing solutions into the distal tubule regularly elicited a decrease in SNGFR, whereas similar injections of Nacontaining solutions did not. In contrast, in experiments on the isolated kidney, Nizet (12-14) concluded that there was no specific effect of increased Na+ or Cl-concentration on renal vascular resistance but that the GFR varied in direct proportion to tubular fluid reabsorption. To settle these differences between the responses of the isolated kidney...

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“…When the macula densa senses a decline in the delivery of NaCl to the distal tubule, it signals the afferent arteriole to dilate, which raises glomerular capillary hydraulic pressure and glomerular filtration rate and thus increases renal tubular flow and sodium delivery to the distal tubule. Increased distal NaCl delivery constricts the afferent arteriole, lowers capillary hydraulic pressure, slows glomerular filtration rate, and diminishes tubular flow (35,56). Tubuloglomerular feedback can be regulated by a number of factors, including ANG II (40), adenosine (47), arachidonic acid metabolites (24), ATP (20), atrial natriuretic factor (19), nitric oxide (NO) (28,30), and superoxide (O 2 Ϫ ) (31).…”

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confidence: 99%

Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase

Liu

Garvin

Ren

et al. 2007

American Journal of Physiology-Renal Physiology

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Liu R, Garvin JL, Ren YL, Pagano PJ, Carretero OA. Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase. Am J Physiol Renal Physiol 292: F1867-F1872, 2007. First published March 6, 2007; doi:10.1152 doi:10. /ajprenal.00515.2006 Ϫ ) enhances tubuloglomerular feedback by scavenging nitric oxide at the macula densa. However, the singling pathway of O 2 Ϫ production in the macula densa is not known. We hypothesized that the increase in tubular NaCl concentration that initiates tubuloglomerular feedback induces O 2 Ϫ production by the macula densa via NAD(P)H oxidase, which is activated by macula densa depolarization. We isolated and microperfused the thick ascending limb of the loop of Henle and attached macula densa in rabbits. A fluorescent dye, dihydroethidium, was used to detect O 2 Ϫ production at the macula densa. When luminal NaCl was switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, O 2 Ϫ production significantly increased. To make sure that the shifts in the oxyethidium/dihydroethidium ratio were due to changes in O 2 Ϫ , we used tempol (10 Ϫ4 M), a stable membrane-permeant superoxide dismutase mimetic. With tempol present, when we switched from 10 to 80 mM NaCl, the increase in oxyethidium/dihydroethidium ratio was blocked. To determine the source of O 2 Ϫ , we used the NAD(P)H oxidase inhibitor apocynin. When luminal NaCl was switched from 10 to 80 mM in the presence of apocynin, O 2 Ϫ production was inhibited by 80%. To see whether the effect of increasing luminal NaCl involves Na-K-2Cl cotransporters, we inhibited them with furosemide. When luminal NaCl was switched from 10 to 80 mM in the presence of furosemide, O 2 Ϫ production was blocked. To test whether depolarization of the macula densa induces O 2 Ϫ production, we artificially induced depolarization by adding valinomycin (10 Ϫ6 M) and 25 mM KCl to the luminal perfusate. Depolarization alone significantly increases O 2 Ϫ production. We conclude that increasing luminal NaCl induces O 2 Ϫ production during tubuloglomerular feedback. O 2 Ϫ generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization. tubuloglomerular feedback TUBULOGLOMERULAR FEEDBACK refers to a negative feedback loop between the epithelial cells of the macula densa and the vascular smooth muscle cells of the afferent arteriole. Tubuloglomerular feedback regulates distal tubular sodium load by adjusting glomerular filtration rate in response to signals received from the macula densa. When the macula densa senses a decline in the delivery of NaCl to the distal tubule, it signals the afferent arteriole to dilate, which raises glomerular capillary hydraulic pressure and glomerular filtration rate and thus increases renal tubular flow and sodium delivery to the distal tubule. Increased distal NaCl delivery constricts the afferent arteriole, lowers capillary hydraulic pressure, slows glomerular filtration rate, and diminishes tubular flow (35,56 ) (31). Enhanced tubu...

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Influence of perfusate osmolality on stop-flow pressure feedback responses in the dog

Cited by 17 publications

References 0 publications

Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

Regulation of Renal Blood Flow by Plasma Chloride

Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase

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