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J Schnermann

Publications and source records attributed to J Schnermann.

At least 91 records · Page 5Linked to original sources
PubMed1986

Tubuloglomerular feedback and glomerular morphology in Goldblatt hypertensive rats on varying protein diets.

The present experiments were performed to examine the effect of variation in protein intake on renal function and morphology in the non-clipped kidneys of Goldblatt hypertensive rats. After renal artery clipping, rats were put on diets containing 5 (LP), 17.5 (NP), or 51% (HP) protein. After 4 to 5 weeks, all rats had developed hypertension. GFR was directly correlated with protein intake (1.47 +/- 0.15 in HP, 1.19 +/- 0.14 in NP, and 0.93 +/- 0.08 ml/min in LP), as was SNGFR (44.2 +/- 1.89, 39.1 +/- 2.23, and 27.9 +/- 0.86 nl/min in HP, NP, and LP rats). The response of SNGFR to changes in loop of Henle flow rate was attenuated in NP and HP rats: the maximum decrease was reduced (30.0 +/- 5.2% in NP, 22.1 +/- 4.2% in HP) and higher tubular flow rates were required to elicit responses (V1/2, the flow rate at which the response is half-maximum, was 28.9 +/- 2.6 nl/min in NP and 28.2 +/- 1.4 nl/min in HP). In LP rats, the maximum response was a decrease of 47.7 +/- 2.5%, and V1/2 was 18.1 +/- 1.2 nl/min, values similar to those found in normal control rats. The weights of the non-clipped kidneys were 0.96 +/- 0.04 g (LP), 1.06 +/- 0.05 g (NP), and 1.36 +/- 0.06 g (HP). In the LP rats there was no difference between the non-clipped and clipped kidneys. Light microscopic evaluation showed a high incidence of focal glomerulosclerosis in non-clipped kidneys of HP rats, but no glomerular lesions in the non-clipped kidneys of LP rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Tubuloglomerular feedback responses with native and artificial tubular fluid.

Experiments were performed to compare the tubuloglomerular feedback response to native and artificial tubular fluid. The change in early proximal flow rate produced by changes in loop of Henle flow rate was measured in anesthetized rats using micropuncture techniques. Loop perfusion fluid was either an artificial solution with an electrolyte composition similar to that of proximal fluid (ATF) or native tubular fluid (NTF) collected from the late proximal tubule. In control rats, in rats on a low NaCl diet, in rats on restricted food intake, and in acutely saline-expanded rats no differences were detected between ATF- and NTF-perfused nephrons. In rats receiving 10 g NaCl/100 g, diet, responses with ATF and NTF to a flow change from 0 to 15 nl/min did not differ significantly; maximum feedback responses (flow change from 0 to 40 nl/min) were, however, significantly greater with ATF (-25.4%) than NTF (-12.9%). Chloride absorption was not different with the two perfusates. With both ATF and NTF a significant negative correlation was found between maximum responses and NaCl intake, with the slope being steeper with NTF. We conclude that some unidentified constituent of tubular fluid affects maximum feedback responses during very high NaCl intake, but feedback responses to physiological flow rate changes appear to be independent of luminal factors.

Animals↗
PubMed1986

Macula densa control of renin secretion and glomerular vascular tone: evidence for common cellular mechanisms.

The macula densa is believed to function as a sensor for control of intrarenal vascular tone and renin secretion. Increases in flow rate through the loop of Henle or increases in distal tubular fluid NaCl concentration result in an increase in local vascular tone and a decrease in glomerular filtration rate, the tubuloglomerular feedback (TGF) mechanism. Increases in distal NaCl concentration are also believed to inhibit renin secretion. Evidence will be reviewed that suggests that these two processes may be activated concurrently and may share common cellular mechanisms. Similarities in the sensor step include a similar pattern of ion specificity, with both responses being relatively anion specific but showing little cation specificity. TGF responses are inhibitable by furosemide, and the renin secretion produced by furosemide seems to be in part macula densa dependent. There appear also to be common features in the effector step of both responses. Increases in intracellular calcium are implicated in both the vasoconstrictive response seen with increased macula densa NaCl concentration and in inhibition of renin secretion. Changes in cyclic AMP may play a role in the converse responses.

Adenosine↗
PubMed1986

Role of the renin-angiotensin system in tubuloglomerular feedback.

The link between the renal tubule and glomerular vasculature comprised of the juxtaglomerular apparatus appears to serve two functions: the regulation of filtration rate and of renin secretion. Elevation of macula densa NaCl concentration stimulates a vasoconstrictor response, which results in a fall in filtration rate, a response that has been termed tubuloglomerular feedback (TGF). Simultaneously, renin secretion is suppressed. The two responses appear to be initiated by a furosemide-sensitive transport step probably located in the macula densa. Both show a pattern of anion specificity identical to Na/K/Cl cotransport mechanisms. An increase in intracellular calcium in the effector cells, the vascular smooth muscle, and the renin-containing granular cells is a likely effector mechanism for both reactions. Angiotensin probably does not mediate the vasoconstrictive feedback response, because changes in local (intracellular) angiotensin concentration would have to be opposite from systemic changes. However, acute changes in angiotensin levels appear to be an important modulator of the magnitude of the TGF response.

Angiotensin II↗
PubMed1985

Dopamine receptor antagonists inhibit the natriuretic response to atrial natriuretic factor (ANF).

The diuretic and natriuretic response of anesthetized rats to low doses of semi-purified atrial extracts or synthetic alpha-hANP was completely blocked by intravenous injection of 50 micrograms of haloperidol or chlorpromazine. Sulpiride or metoclopramide at the same doses did not show this effect. We conclude from these results that dopamine receptors, probably of the D1-type, are involved in the natriuretic effect of the atrial peptides.

Adenylyl Cyclases↗
PubMed1984

Tubuloglomerular feedback, prostaglandins, and angiotensin in the autoregulation of glomerular filtration rate.

To define the mechanisms responsible for autoregulation of SNGFR in the subnormal pressure range, the response of SNGFR to graded reductions of arterial pressure was measured before and after interfering with the tubuloglomerular feedback system (TGF), angiotensin II action and prostaglandin (PG) synthesis. Studies were performed in male Sprague-Dawley rats in which estimated surgical plasma losses were replaced, because euvolemic animals were found to have better autoregulatory capacity than hydropenic animals. In control plasma-replaced animals, a pressure reduction from normal to 97.5 mm Hg and a further reduction to 78 mm Hg had no significant effect on SNGFR (31.8 +/- 1.32 to 31.7 +/- 1.6 to 29.3 +/- 1.48 nl/min) when all autoregulatory mechanisms were intact. After eliminating TGF, the same pressure steps were followed by significant reductions in SNGFR (40.8 +/- 1.75 to 36.4 +/- 2.18 to 31.0 +/- 1.56 nl/min). During infusion of saralasin (1 microgram/kg X min), SNGFR did not change significantly during reduction of pressure from normal to 95.5 mm Hg (32.0 +/- 1.02 to 30.7 +/- 1.58 nl/min) but fell when pressure was reduced to 77 mm Hg (26.0 +/- 1.19 nl/min). Infusion of this dose of saralasin was without significant effect on the response of early proximal flow rate to loop of Henle perfusion. During indomethacin-induced inhibition of PG synthesis, SNGFR fell significantly in response to both pressure steps (38.6 +/- 1.4 to 34.0 +/- 1.68 to 25.5 +/- 1.29 nl/min). An analysis of the autoregulatory components indicates that in the higher pressure interval 115 to 95 mm Hg, TGF contributes about 50% and PG's about 30% to autoregulatory adjustments. In the lower pressure interval, 95 to 78 mm Hg, 30% autoregulatory compensation occurs through the TGF mechanism and 20% depends upon the action of angiotensin II. Probably in part by interfering with both of those mechanisms, inhibition of PG synthesis reduces autoregulatory compensation by about 60%.

Animals↗
PubMed1984

Inactivation of atrial natriuretic substance by kallikrein.

To further characterize the properties of the potent natriuretic and diuretic substance that can be extracted from atrial tissue, we investigated its susceptibility to inactivation by kallikrein and other proteolytic enzymes. Extracts of rat atrial tissue (tissue wet wt 100 mg/ml) were incubated with enzymes under standard conditions and tested by injection into nondiuretic anesthetized rats. One hour of incubation at 37 degrees C with pure porcine pancreatic kallikrein at concentrations of 250 micrograms/ml or greater significantly reduced the activity of atrial natriuretic substance. The reduction in activity was dependent on both enzyme concentration and time of incubation. The kallikrein-catalyzed degradation was completely blocked by aprotinin but was only partially retarded by soybean trypsin inhibitor. Trypsin reduced natriuretic and diuretic activity of extracts at concentrations of 400 micrograms/ml or greater, with nearly complete inactivation at a concentration of 1,000 micrograms/ml. Carboxypeptidase B also caused a concentration-dependent inactivation of the natriuretic material. Last, alpha-chymotrypsin (1,000 micrograms/ml) and elastase (1,000 micrograms/ml) were found to destroy the natriuretic activity. In a separate set of experiments natriuretic activity was observed to be retained by a 1,000 mol wt cutoff membrane. Inactivation of the natriuretic peptide by renal kallikrein is a possible mechanism for in vivo regulation of natriuretic activity.

Animals↗
PubMed1984

Quantitative characterization of the tubuloglomerular feedback response: effect of growth.

Studies were performed to characterize quantitatively the effect of changing loop of Henle flow rate on single nephron glomerular filtration rate (SNGFR) in male Sprague-Dawley rats of varying body weight. Rats weighing 100, 220, and 350 g were studied using standard renal micropuncture techniques. The relationship between loop of Henle flow rate (VLP) and SNGFR was characterized for individual nephrons by multiple determinations of SNGFR during loop perfusion. An inverse sigmoidal relationship was observed that could be described as delta SNGFR = a/(1 + ek(b-VLP], where delta SNGFR is the change in SNGFR from the value measured at zero loop flow, a is delta SNGFRmax, the maximum change, b is V1/2, the flow rate at which the response is half maximum, and k is [4f' (V1/2)]/a with f' (V1/2) the slope at V1/2. delta SNGFRmax increased with increasing body size (7.9 +/- 1.16, 18.9 +/- 0.90, and 25.2 +/- 2.73 nl/min, respectively, in the three groups), and the curve shifted to the right (V1/2 = 10.3 +/- 0.8, 15.4 +/- 0.83, and 22.3 +/- 1.22 nl/min). The maximum slope increased (f' (V1/2) = 0.9 +/- 0.19, 1.7 +/- 0.16, and 3.2 +/- 0.70), but the exponential constant k was uninfluenced by growth. Independent of rat size, a 10% increase in loop flow at the midpoint produced at 5-10% decrease in SNGFR. Free-flow values of SNGFR and VLP were found to lie in the most sensitive range of the feedback curve.

Animals↗
PubMed1984

Opposing effects of captopril and aprotinin on tubuloglomerular feedback responses.

We investigated the effect of two protease inhibitors, captopril and aprotinin, on tubuloglomerular feedback. In anesthetized rats, 15 or 25 mg/kg captopril significantly reduced the change of early proximal flow rate achieved by raising loop of Henle perfusion rate from 0 to 40 nl/min. Consistent with this reduction of maximum responses, there was a rise of single nephron glomerular filtration rate from 30.7 +/- 1.15 to 35.0 +/- 0.93 nl/min (P less than 0.01) following 25 mg/kg captopril. Infusion of aprotinin at 40,000 KIU/h produced an increase in maximum feedback responses from 38.2 +/- 1.66 to 56.8 +/- 2.35% (P less than 0.05). Infusion of aprotinin in two different doses (20,000 or 40,000 KIU/h) diminished or prevented the effect of 25 mg/kg captopril on maximum feedback responses. Since the main action of aprotinin is believed to be kallikrein inhibition, our data suggest that the magnitude of feedback responses may be affected by the kallikrein-kinin system and that the action of captopril may be in part mediated by its interference with kinin metabolism.

Absorption↗
PubMed1982

Micropuncture studies of the renal effects of atrial natriuretic substance.

Micropuncture studies of the renal effects of atrial natriuretic substance. Injection of atrial extract produced by homogenization, boiling and centrifugation of atrial tissue from one heart caused a 10fold increase in urine flow rate and a 30-fold increase in Na excretion. Similarly prepared extracts of ventricle were without effect. To identify the site of action of atrial natriuretic substance, extract was infused intravenously at rates corresponding to 3 or 6 atria per hour. During infusion at a rate of 3 atria per hour mean urine flow increased from 9.5 +/- 2.8 to 17.2 +/- 1.2 microliter/min and Na excretion from 0.14 +/- 0.06 to 1.78 +/- 0.14 mumol/min. Glomerular filtration rate (GFR), single nephron filtration rate (SNGFR) and proximal and loop of Henle fluid absorption did not change significantly. During infusion of 6 atria per hour, paralleling a greater rise in urine flow rate (from 6.4 +/- 2.09 to 40.3 +/- 7.5 microliter/min) and in sodium excretion (from 0.18 +/- 0.0008 to 5.97 +/- 0.93 mumol/min), filtration rate, measured for either the single nephron or the whole kidney, rose. As a consequence of the rise in GFR, delivery of fluid and chloride into the distal tubule increased significantly. These data suggest that to a major extent the natriuresis is caused by transport inhibition along collecting tubules and collecting ducts. In addition, at high doses a rise in filtration rate contributes to the natriuretic effect of atrial extracts.

Animals↗
PubMed1982

Further evidence for an inverse relationship between macula densa NaCl concentration and filtration rate.

It has been concluded that tubulo-glomerular feedback mechanism is triggered by changes in NaCl concentration ([NaCl]) at the macula densa. This conclusion is based on the demonstration that changes in filtration rate produced during retrograde perfusion of the loop of Henle depend upon the perfusate [NaCl]. Experiments were performed to evaluate whether the effect on glomerular function of orthograde perfusion of the loop of Henle is consistent with this conclusion. Early proximal flow rate (VEP), stop-flow pressure (PSF), early distal chloride concentration ([C]), and flow rate were measured during perfusion of the loop of Henle with mannitol solution (300 mosm kg-1), 30mM NaCl + mannitol (300 mosm kg-1), 140 mM Na isethionate and artificial tubular fluid. When distal flow exceeded 10 nl min-1, the magnitude of the glomerular response was predictable from the [Cl]. The linear regression line, delta VEP = -0.27 [Cl] + 4.3, did not differ from that obtained previously with the retrograde technique. Retrograde perfusion with 140 mM Na isethionate was without effect on VEP. We conclude that the effect on glomerular function of perfusion of the loop of Henle in either an orthograde or a retrograde direction with these solutions depends upon the chloride concentration at the macula densa.

Animals↗
PubMed1982

Reversal of indomethacin-induced inhibition of tubuloglomerular feedback by prostaglandin infusion.

Experiments were performed in rats to study the effect of infusion of PGI2, PGE2, and PGF2 alpha on tubuloglomerular feedback responses (i.e. the change of SNGFR in response to a change of loop of Henle flow rate) in the presence and absence of simultaneous inhibition of endogenous PG synthesis with indomethacin. Infusion of PGI2 or PGE2 at rates that did not alter arterial blood pressure did not significantly modify the magnitude of feedback responses (PGI2 8.5 micrograms/hr, PGE2 85 micrograms/hr). Some inhibition of feedback responses was seen when PGI2 and PGE2 were administered at higher rates that were associated with a reduction of blood pressure (PGI2 20 micrograms/hr, PGE2 200 micrograms/hr). PGI2 (8.5 micrograms/hr) and PGE2 (85 micrograms/hr) largely prevented feedback inhibition induced by indomethacin. When given subsequent to indomethacin PGI2 and PGE2 restored feedback responsiveness almost to normal. In contrast, PGF2 alpha did not influence feedback inhibition caused by indomethacin. Infusion of PGI2 induced partial restoration of feedback responses in DOCA-salt treated animals in which the feedback system is virtually completely inactive. Our results indicate that availability of PGI2 or PGE2 is necessary for the normal operation of the tubuloglomerular feedback mechanism for control of nephron filtration rate.

Animals↗
PubMed1982

Concentration-dependent sodium chloride transport as the signal in feedback control of glomerular filtration rate.

There is good evidence that the initial step leading to a feedback response is the concentration-dependent active transport of sodium chloride across the macula densa cells. This may lead to changes in sodium chloride concentration or tonicity in the small and relatively unstirred compartment of the juxtaglomerular interstitium or to changes in the concentration of transport-related compounds or metabolites. We assume that the Goormaghtigh cells act as receptor cells that transform such compositional changes into a signal propagating to the glomerular vascular elements.

Animals↗
PubMed1981

The early phase of experimental acute renal failure. VI. The influence of furosemide.

Experiments were performed to determine whether furosemide, given in doses high enough to induce a strong diuresis and to inhibit the mechanism of tubuloglomerular feedback, offers any protection from acute renal failure induced by a nephrotoxin or ischaemia. Microperfusion of the loop of Henle revealed that a tubular furosemide concentration of 5 x 10(-5) mol x 1(-1) was necessary to fully inhibit the tubuloglomerular feedback response to a raised sodium chloride concentration at the macula densa. The infusion of furosemide systemically to achieve such concentrations in the tubule resulted in an improvement in renal function when given before or after the nephrotoxin but was without effect when given before or after ischaemia. Measurements of furosemide concentrations in the urine, however, confirmed that sufficient amounts were applied to inhibit the feedback mechanism. It is concluded from this and similar studies that furosemide is only beneficial in models of acute renal failure with an obstructive or nephrotoxic pathogenesis, in which it acts by flushing out the noxious material and not by inhibiting the mechanism of tubuloglomerular feedback.

Acute Kidney Injury↗
PubMed1981

Feedback-mediated reduction of glomerular filtration rate during infusion of hypertonic saline.

An acute rise in plasma sodium concentration from 146 +/- 2.6 to 155 +/- 1.7 was produced in rats by the intraarterial infusion of 0.6 M sodium chloride (0.25 ml/min for 4 min followed by 0.25 ml/hr). A parallel fall in whole kidney GFR (from 0.45 +/- 0.02 to 0.36 +/- 0.04 ml/min per 100 g of body wt) and SNGFR measured in the distal tubule (31.4 +/- 3.01 to 27.9 +/- 2.40 nl/min) was observed. In contrast, proximally measured SNGFR (with feedback interrupted) rose from 32.7 +/- 2.73 to 37.1 +/- 2.84 nl/min. The loop of Henle flow, determined from distal SNGFR and (TF/P) inulin in late proximal fluid collected without interrupting tubular flow, rose from 13.7 +/- 1.50 to 17.0 +/- 1.42 nl/min as a consequence of a fall in proximal reabsorptive rate from 15.8 +/- 1.87 to 11.0 +/- 1.37 nl/min. Intraarterial infusion of hypertonic sodium bicarbonate resulted in comparable increases in plasma sodium concentration and inhibition of proximal reabsorption but did not produce a fall in filtration rate. We conclude (1) acute infusion of hypertonic sodium chloride results in an inhibition of proximal reabsorption and therefore in an increased rate of loop of Henle flow, (2) this increase in flow causes a fall in GFR through the tubuloglomerular feedback mechanism, and (3) acute infusion of hypertonic sodium bicarbonate does not result in a feedback-mediated fall in GFR, presumably because increased delivery of bicarbonate-rich fluid does not activate the feedback mechanism.

Animals↗