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Biomedical subjects

F S Wright

Publications and source records attributed to F S Wright.

At least 91 records · Page 5Linked to original sources

Interference with feedback control of glomerular filtration rate by furosemide, triflocin, and cyanide.

Microperfusion experiments have shown that increases in flow rate of tubule fluid through the loop of Henle are followed by reductions in single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) measured in the proximal tubule of the same nephron. Because changes in luminal sodium concentration are not consistently related to changes in SNGFR and SFP, we explored the possibility that a transport step at a flow-dependent distal-sensing site might be involved in feedback control of SNGFR. Because the macula densa cells of the distal tubule are adjacent to the glomerular vessels of the same nephrons, they could be the distal-sensing mechanism. We perfused superficial loops of Henle from late proximal to early distal segments in three groups of rats while measuring SFP in the proximal tubule of the same nephron, SNGFR in the proximal tubule of the same nephron, or flow rates of fluid, Na, K, and Cl emerging from the perfused loops. Perfusion solutions used were 0.15 NaCl, Ringer or Ringer with one of several inhibitors of electrolyte transport. Perfusion rates were 10 or 40 nl/min (also, zero during measurements of SFP and SNGFR). With Ringer alone the loop-flow rate increased from 10 to 40 nl/min, caused a decrease in SFP from 37.6 to 32.1 mm Hg, and a decrease in SNGFR from 29.9 to 18.7 nl/min. Concentrations of Na, K, and Cl in early distal fluid and absorption of Na and Cl along the loop segment were also increased when loop perfusion rate was increased. Decreasing the perfusion rate to zero had little effect on SFP or SNGFR. The SFP response to increased flow rate did not occur when the perfusion solution contained furosemide (10(-4) M). No reduction of the SFP response was seen with other diuretics tested (amiloride, acetazolamide, ethacrynic acid, mercaptomerin) or with 0.15 M NaCl alone. The SNGFR response to increased perfusion rate was reduced by furosemide, triflocin, and cyanide but not by amiloride. Na and Cl absorption by the perfused segment were inhibited by furosemide, triflocin, cyanide, and amiloride. Amiloride and acetazolamide, probably do not act in the ascending limb. Ethacrynic acid and mercaptomerin are known to be ineffective in rat nephrons. Thus, agents that could have inhibited NaCl absorption by macula densa cells interfered with the feedback mechanism.

Acetazolamide↗

An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron.

The evidence from previous micropuncture studies for an inhibitory effect of furosemide on proximal sodium reabsorption in the rat has been conflicting. Intrinsic reabsorptive capacity, estimated in free flow and shrinking drop experiments, has been reported to be depressed, whereas fractional reabsorption usually remains unchanged. We have recently reported that, during conditions of elevated intraluminal hydrostatic pressure, unless care is taken to prevent retrograde flow of tubule fluid from more distal sites, the concentration of inulin in late proximal fluid is often factitiously elevated. Since furosemide raises intraluminal pressures, often markedly, the failure to detect a depression of fractional reabsorption might be the consequence of retrograde contamination during fluid collection. Experiments were designed to compare the effect of furosemide on fractional sodium reabsorption by the proximal tubule when collections were obtained with distal oil blocks of conventional length as well as with unusually long blocks of oil of low and high viscosities. When reflux is prevented, fractional sodium reabsorption is usually depressed by furosemide, whereas when conventional distal blocks are used, the calculated values for fractional reabsorption either remain unchanged or increase. Simultaneous measurements of nephron glomerular filtration rate indicate that the latter is the consequence of retrograde contamination.

Animals↗