Indomethacin Inhibits Renal Functional Adaptation to Nephron Loss

Hahne, Bengt; Selén, Göran; Erik, A.; Persson, Gunnar

doi:10.1159/000172920

Cited by 18 publications

(18 citation statements)

References 6 publications

(10 reference statements)

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“…This phenomenon has been demonstrated by other authors in chronic situations such as two-kidney, one-clip Goldblatt hypertensive rats, unilateral nephrectomy and trans planted kidneys [Hahne et al" 1984]. Very little attention has been paid to study the functional alteration in the contralateral kid ney to acute unilateral renal arterial constric tion [Murray et al.…”

Section: Discussionmentioning

confidence: 85%

Whole Kidney Response to Reduced Arterial Pressure during Converting Enzyme Inhibition in the Rat

Göransson¹,

Isaksson²,

Sjöquist³

1986

Kidney Blood Press Res

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Autoregulatory efficiency of renal blood flow (RBF) and glomerular filtration rate (GFR) was evaluated in male Sprague-Dawley rats during interference with the renin-angiotensin system by a converting enzyme inhibitor (CEI), captopril (3 mg · h^-1 · kg^-1 BW). RBF and GFR were approximately 25 (p < 0.01) and 20% (p < 0.02) higher, respectively, in rats infused with CEI than in control rats at spontaneous renal arterial pressure (RAP). A reduction of RAP to 100 mm Hg (within the autoregulatory range) resulted in effective autoregulation of GFR and RBF in control rats. In rats given CEI, however, the autoregulation of GFR was markedly impaired. GFR decreased by 35% (p < 0.001), while RBF remained relatively unchanged. This caused the filtration fraction to decrease from 0.33 ± 0.01 to 0.29 ± 0.01 (p < 0.001). RAP had a consistent effect on the urine flow rate, even though both GFR and RBF were well autoregulated in control rats. No significant decrease in electrolyte excretion was detected within the autoregulatory range in control rats, but during converting enzyme blockade this excretion decreased progressively as RAP was reduced, and the decrease correlated well to the reduction in GFR. In summary, these results suggest that the renin-angiotensin system plays an important intrarenal role in the autoregulation of GFR, probably through an efferent arteriolar mechanism. Furthermore, it is demonstrated that the contra-lateral kidney efficiently compensates in urinary electrolyte excretion for an acute unilateral reduction of RAP, both under control conditions when the perfusion pressure to the contra-lateral kidney increased and during blockade of the renin-angiotensin system when the increase in perfusion pressure was inhibited.

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Section: Discussionmentioning

confidence: 85%

Whole Kidney Response to Reduced Arterial Pressure during Converting Enzyme Inhibition in the Rat

Göransson¹,

Isaksson²,

Sjöquist³

1986

Kidney Blood Press Res

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“…These data suggested that prostaglandins (E2 or '2) have a permissive role in the tubuloglomerular feed-back mechanism but are probably not the mediator of the response. In contrast, Hahne et al (1984) reported that indomethacin did not affect tubuloglomerular feed-back in the rat and Boberg et al (1984) and Persson, Hahne & Selen (1983) reported that PGI2 reduced the sensitivity of the tubuloglomerular feed-back in the rat kidney. However, Persson et al (1983) found that PGE2 and 193+52 770+187 * * C is the measurement at the control point.…”

Section: Resultsmentioning

confidence: 93%

Renal vasoconstrictor response to hypertonic saline in the dog: effects of prostaglandins, indomethacin and theophylline.

Gerber¹,

Nies²

1986

The Journal of Physiology

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SUMMARY1. The role of prostaglandins in the mechanism of the tubuloglomerular feed-back was examined in the anaesthetized dog using the infusion of hypertonic saline to increase renal plasma sodium concentration by 30 mmol/l as the stimulus to activate the tubuloglomerular feed-back.2. Two sequential infusions of hypertonic saline into the renal artery for 10 min separated by 90 min resulted in equivalent reductions in renal blood flow (264+ 32 to 174 + 20 ml/min first time; 280 + 29 to 200 ± 15 ml/min second time).3. Administration of indomethacin, 8 mg/kg, between the two infusions did not alter the renovascular response to hypertonic saline (319 + 26 to 226 + 35 ml/min vs. 288 + 32 to 202 + 24 ml/min).4. Infusion of either prostaglandin E2 (PGE2) or prostaglandin '2 (PGI2) during the second hypertonic saline infusion period also resulted in no change in the renovascular response (251 + 37 to 141 + 31 ml/min vs. 297 +53 to 184+ 51 ml/min; and 223 + 31 to 162 + 35 ml/min vs. 254 + 33 to 186 + 39 ml/min, respectively).5. Intrarenal theophylline, to a concentration of 40 ,sg/ml, however, totally abolished the renovascular response to hypertonic saline (279 ± 20 to 209+ 13 ml/min control vs. 390 + 26 to 402+ 17 ml/min during theophylline).6. The systemic hypertensive response during the infusion of hypertonic saline was unaltered by indomethacin or prostaglandins but was totally abolished by theophylline.7. Our data suggest that prostaglandins do not have a role in either mediating or modulating the tubuloglomerular feed-back mechanism in the canine kidney; however, intrarenal adenosine has a critical role in the mediation of renal vasoconstriction as well as the systemic hypertension during the activation of the tubuloglomerular feed-back by intrarenal infusion of hypertonic saline.

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“…Likewise, the response is blunted, but not abolished, by blockade of cyclooxygenase with indomethacin (indo) or meclofenamate (4)(5)(6). Simultaneous blockade of AII generation and PG production with captopril and meclofenamate abolishes TGF-induced changes in glomerular capillary hydrostatic pressure although some changes in single nephron GFR (SNGFR) persist (7l).…”

Section: Introductionmentioning

confidence: 99%

“…Indo inhibits cyclooxygenase and reduces the production of all PGs including PGI2 and TX (4,6,7). Indo (2.5 mg -ml-', Sigma Chemical Co.) was dissolved in 1 M Na2CO3 solution and given to group 2 rats to assess the effects of nonselective inhibition of production ofboth vasodilator and vasoconstrictor PGs on the TGF response.…”

Section: Introductionmentioning

confidence: 99%

Modulating role for thromboxane in the tubuloglomerular feedback response in the rat.

Welch

Wilcox²

1988

J. Clin. Invest.

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Sbme studies have indicated that PGs can modulate the single nephron tubuloglomerular feedback (TGF) response. The aim of this study was to define the specific role of the vasoconstrictor PG, TX, by administration to rats of either vehicle (group 1; n = 20) or drugs that inhibit either cyclooxygenase (indomethacin lindol, 5 mg * kg-', group 2, n = 17), TX synthetase 485 [UK], 100 mg kg-', group 3, n = 19), or TX receptors 548 [SQJ, group 4, n = 14,953 [L, 50 mg. kg-', group 5, n = 8). Indo reduced excretion of the prostacyclin derivative 6-keto-PGF14, and TXB2 and lowered whole kidney GFR and renal plasma flow, whereas UK lowered excretion of TXB2 only and did not change basal renal hemodynamics. The TGF response (assessed from reduction in proximal tubule stop-flow pressure (Pf, mmHg) during increases in perfusion of the loop of Henle (LH) from 0 to 40 nl* min-') was unchanged after vehicle (9.8±0.5-10.9±1.0, NS) but blunted (P < 0.001) by 40-65% in rats of groups 2-5 (indo, 11.1±1.0-4.4±0.7; UK, 9.0±0.8-4.8±0.7; SQ, 10.3±0.6-4.8±0.6; L, 10.7±0.5-6.7±13). This blunting was due to lower values for Pdf at zero LH flow after indo, SQ, and L, and higher values of Pf at 40 nl. min'1 LH flow after indo and UK. The fall in single nephron GFR (SNGFR, nl min-1) with increasing LH perfusion was unchanged after vehicle (10.9±2.8-11.2±0.8) but was blunted (P < 0.05) by 45-55% in rats given indo (13.9±1.2-6.2±2.2) or UK (12.8±2.1-7.0±1.5). UK produced dose-dependent reductions in TXB2 excretion (IC50, 15 mg * kg-lJ and inhibition of the TGF response (IC5o: 30 mg-kg-'). After blockade of TX receptors by SQ, UK had no further affect on the TGF response. The fall in Pf at high LH flow was blunted (P < 0.05) by indo and UK, whereas the rise in Pf at zero LH flow was blunted by indo, SQ, and L.

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Indomethacin Inhibits Renal Functional Adaptation to Nephron Loss

Cited by 18 publications

References 6 publications

Whole Kidney Response to Reduced Arterial Pressure during Converting Enzyme Inhibition in the Rat

Whole Kidney Response to Reduced Arterial Pressure during Converting Enzyme Inhibition in the Rat

Renal vasoconstrictor response to hypertonic saline in the dog: effects of prostaglandins, indomethacin and theophylline.

Modulating role for thromboxane in the tubuloglomerular feedback response in the rat.

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