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Biomedical subjects

J Schnermann

Publications and source records attributed to J Schnermann.

At least 109 records · Page 6Linked to original sources
PubMed1981

Localization, mediation and function of the glomerular vascular response to alterations of distal fluid delivery.

Direct assessment of glomerular hemodynamics revealed that elevation of loop of Henle flow induces a significant increase of afferent arteriolar resistance. Examination of glomerular poles of normo- and hyperperfused nephrons by light microscopy supports this result by demonstrating significantly narrowed luminal diameters of afferent arterioles in the hyperperfused tubules. Thus, the decrease of glomerular filtration rate and glomerular capillary pressure induced by activating tubuloglomerular feedback is caused predominantly by vasoconstriction of the afferent arterioles. It is possible that the feedback-induced change of vasomotor tone is related to the action of locally generated angiotensin II. However, the pertinent experimental evidence does not appear to be internally consistent with this notion. Observations that methylxanthines, prostaglandin synthesis inhibitors, and beta-adrenergic blocking agents interfere with the initiation of normal feedback responses suggest that the vascular reaction is caused by a complex system of interdependent components. Constancy of nephron filtration rate during acute changes of arterial pressure is observed in rats when tubuloglomerular feedback is operative. In contrast, during acute and chronic interruption of feedback transmission, nephron GFR varies with blood pressure. While an intact feedback system is necessary for complete autoregulation of nephron GFR, calculation of the predicted dependency of GFR upon pressure reveals that some residual autoregulatory capacity remains even without a functional feedback system. It is concluded that, in addition to tubuloglomerular feedback, other mechanisms participate in GFR autoregulation.

Animals↗
PubMed1980

Failure of tubule fluid osmolarity to affect feedback regulation of glomerular filtration.

Experiments were performed in Sprague-Dawley rats in order to distinguish between sodium chloride and total solute concentration as possible luminal signals capable of eliciting tubuloglomerular feedback responses. Early proximal flow rate (VEP), an index of nephron filtration rate, was measured without perfusion of the loop of Henle and during retrograde perfusion with solutions containing 20, 35, 60 to 100 mM NaCl and varying amounts of either urea or mannitol to achieve total solute concentrations of 130, 280, or 400 mosM. Perfusion flow rate was kept constant at 20 nl/min. Perfusion with a solution containing 20 mM NaCl and made hypo-, iso-, or hypertonic with urea or mannitol caused little or no change in VEP. Perfusion with a 35 mM NaCl solution made hypo-, iso-, or hypertonic with mannitol resulted in a fall of VEP of 6-7 nl/min. When NaCl concentration was 60 mM, VEP fell by 10-14 nl/min with solutions made hypo-, iso-, or hypertonic with urea or mannitol. With 100 mM NaCl solutions made hypo-, iso-, or hypertonic with mannitol, VEP fell approximately 12 nl/min. These results indicate that feedback responses are determined by the NaCl concentration of the perfusate and that this NaCl dependency is not modified by varying perfusate osmolarity between 130 and 400 mosM with urea or mannitol as osmotic agents.

Animals↗
PubMed1979

Formation and action of prostaglandins in the kidney.

The kidney has a high capacity to produce a spectrum of different acting prostaglandins (PG). In vivo and in vitro studies have shown that renal formation of PG's, possibly in the vasculature of the cortex represents an essential step in the mechanisms regulating the secretion of renin. PG's formed in the cortex seem to participate also in the control of renal vascular resistance and glomerular filtration rate. PGE2 formed in the medulla modulates the hydroosmotic action of antidiuretic hormone and influences the kidney's capacity for urine concentration. Renal PG formation is reduced by high NaCl intake and enhanced by low NaCl intake and in hypokalemic states. These findings make renal PG's good candidates for participation in the regulation of salt and water balance and in the control of blood pressure. Due to the close connection with the renin angiotensin system, alterations in renal PG formation might be involved in the etiology of high and low renin states. Thus, an impairment in the renal cortical production of vasodilating and renin-stimulating PG's could constitute the common denominator for both the reduced renin secretion and the increased vascular resistance which have been reported to be associated in essential hypertension.

Animals↗
PubMed1979

Feedback regulation of nephron filtration rate during pharmacologic interference with the renin-angiotensin and adrenergic systems in rats.

Tubuloglomerular feedback has been defined as a mechanism in which changes in distal tubular sodium chloride delivery induce changes in glomerular arteriolar resistance. Experiments were performed in rats to test the hypothesis that the alterations in vasomotor activity are controlled by local hormonal mechanisms. Early proximal flow rate (EPFR), used as an index of filtration rate, was assessed at loop perfusion rates of 10 and 40 nl/min and during zero loop flow before and during intravenous administration of agents which interfere with the reninangiotensin or adrenergic systems. During infusion of the angiotensin (A) antagonists [Sar1,Ile8-]-AII or [Me2,Gly1,Ile8]-AII at doses ranging from 4.8 to 30.6 micrograms/kg . min, feedback response, expressed as percent change of EPFR during loop flow elevation from 3 to 40 nl/min, fell from a mean of 47.6 +/- 3.3% to 33.2 +/- 2.9% (P less than 0.05). Likewise, after administration of the converting enzyme inhibitor SQ 20881 in a dose ranging between 5.5 and 34.0 mg/kg, feedback response decreased from 48.5 +/- 2.1% to 25.9 +/- 1.9% (P less than 0.001) and returned to 43.1 +/- 5.1% after the inhibitory effect of SQ 20881 on the pressure response to angiotensin I had disappeared. Luminal application of [Sar1,Thr2]-AII (5mM) or of SQ 20881 (5 or 10 mM) had no effect on the feedback response. A significant reduction in the feedback response was noted also during intravenous infusion of propranolol (46.4 +/- 3.2% vs. 29.0 +/- 2.8%, P less than 0.001), whereas 6-OH-dopamine, reserpine, or phenoxybenzamine had no detectable effect. Our results are in agreement with the concept that the renin-angiotensin system may mediate feedback-induced resistance changes. In addition, circulating catecholamines may, in some unknown manner, act as modulators of the feedback response.

Adrenergic alpha-Antagonists↗
PubMed1979

Feedback mediation of SNGFR autoregulation in hydropenic and DOCA- and salt-loaded rats.

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.

Absorption↗
PubMed1978

Prostaglandin (PG) analysis in urine of humans and rats by different radioimmunoassays: effect on PG-excretion by PG-synthetase inhibitors, laparotomy and furosemide.

The radioimmunological (RIA) determination of prostaglandin (PG) E2 and of PGF2alpha in urine of humans and rats is described in detail. After extraction and chromatography PGE2 was determined by using a PGE specific antibody or by using either PGB or PGF2alpha specific antibodies after the respective conversion procedures. The three different RIA procedures were compared to each other. PGF2alpha was determined by a specific antibody to PGF2alpha. Basal excretion of PGE2 and of PGF2alpha in healthy women on free diet was 9.3 ng/hour+/-0.98 and 18.3 ng/hour +/- 2.5 respectively. Furosemide increased the excretion of PGE2 and of PGF2alpha in humans significantly, while PG-excretion rates decreased on indomethacin. In rat urine PGE2 and PGF2alpha increased markedly from 46.2 pg/min +/- 9.3 and 27+/- 3.4 to 253.8 +/- 43.3 and 108 +/- 12.6 pg/min (per one kidney) in the anesthetized-laparotomized animal. This increase was abolished after giving two different PG synthetase inhibitors.

Adult↗
PubMed1977

Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney.

Microperfusion experiments were performed in rats to assess the effect of luminal application of theophylline and the more lipophilic 3-isobutyl-1-methylxanthine (IBMX) on feedback regulation of glomerular filtration rate. Elevation of loop of Henle flow from 0 to 40 nl/min caused a 20.3 +/- 4.5% reduction of stop flow pressure (SFP) and a 32.2 +/- 3.7% reduction of early proximal flow rate (EPFR) when the perfusate was a 140 mM NaCl solution. When theophylline was added in a concentration of 5mM SFP fell by only 5.3 +/- 1.8% and EPFR by 7.9 +/- 33%, changes which were significantly smaller than in the control perfusions (P less than 0.01). An identical change of loop of Henle flow in the presence of IBMX in concentration of 1 and 5 mM was associated with a 4.5 +/- 3.9% decrease and a 12.1 +/- 2.7% increase of EPFR. In orthograde perfusion experiments full inhibition of the feedback response was noted at an IBMX concentration of about 1 mM while during retrograde perfusion a concentration of 0.4 mM was sufficient to produce the same effect. This indicates that methylxanthines diffuse out of the loop of Henle to a considerable extent. Methylxanthines reduced absolute and fractional water absorption along the loop of Henle to some extent while Cl absorption rates and early distal Cl concentrations were not significantly altered. Cyclic AMP applied from the luminal side in a concentration of 10 mM did not affect the feedback response of EPFR to flow elevation from 0 to 40 nl/min. Luminal application of dibutyryl cyclic AMP at 10 mM induced a small, but significant reduction of the feedback response when tested by paired t-test (P less than 0.05). Our results show that luminal application of methylxanthines strongly interfere with feedback regulation of glomerular filtration rate. It is unclear at present whether this effect is related to inhibition of cyclic nucleotide phosphodiesterase and a rise in tissue cyclic AMP levels or to interference with a mechanism involving the local action of adenosine or 5'-AMP.

Animals↗
PubMed1977

Feedback control of glomerular filtration rate in isolated, blood-perfused dog kidneys.

Micropuncture studies were done in isolated, blood-perfused dog kidneys to investigate the intrarenal nature of tubuloglomerular feedback regulation of nephron filtration rate. Collections were made at early proximal tubular sites during alterations in flow through the loop of Henle to elicit the feedback response. Renal blood flow in the 10 isolated kidneys averaged 4 ml/ min-g kidney after an initial vasoconstriction. Filtration rate was 0.52 +/- 0.12 ml/min-g kidney for the period 90-120 min, but progressively fell after 120 min, as did fractional sodium reabsorption and PAH extraction. The feedback regulation of nephron filtration rate was demonstrated during the first 3 hrs of perfusion even with subnormal renal function. The feedback response expressed as the percent reduction of early proximal flow rate when loop of Henle flow was elevated from 0 to 45 nl/min was 41.3 +/- 4.5 (for the first 90 min), 35.3 +/- 7.5 (90-120 min), 24.3 +/- 6.8 (120-150 min), and 26.6 +/- 7.7% (150-180 min). After 180 min, the feedback response was no longer demonstrated. These results show that feedback-induced changes in nephron filtration rate are achieved in the absence of nervous system influences.

Animals↗
PubMed1976

Activation of tubulo-glomerular feedback by chloride transport.

To define the luminal agent(s) responsible for the reduction of nephron filtration rate following increases of loop of Henle flow rate early proximal flow rate (EPFR) during loop perfusion with 17 different salt solutions were compared to the non-perfused tubules. During orthograde microperfusions a reduction of EPFR as indication of a feedback response was noted with a number of monovalent Cl- and Br- salts (LiCl, KCl, NaCl, RbCl, CsCl, NH4Cl, choline Cl, NaBr, KBr), with Na+ salts except Na acetate (NaHCO3, NaNO3, NaF, NaI, NaSCN), and with CaCl2 and MgCl2. These latter 2 solutions where used in a concentration of 70 mM while all other solutions had a concentration of 140 mM. During retrograde perfusion from the distal to the proximal end of the loop of Henle EPFR fell significantly with Cl- and Br- salts with percentage changes of EPFR ranging from -8.0 to -44.3%. In contrast, Cl- free salts and Cl- salts of divalent cations were associated with percentage changes of EPFR ranging from +7.1 to -6.2%, significance being reached only during perfusion with NaSCN. When furosemide (5 x 10(-4) M) was added to NaBr or KBr a feedback response was not observed. During orthograde perfusion with NaNO3 distal Cl- concentrations were 44.2 +/- 5.08, mM (mean +/- S.E.) at a perfusion rate of 10 nl/min and 59.1 +/- 3.93 mM at a rate of 40 nl/min. CaCl2 perfusion induced a marked elevation of distal Cl- concentrations to levels higher than 140 mM. Loop chloride handling was normal during RbCl perfusion. The magnitude of the feedback response during retrograde perfusion was not changed by lowering NaCl concentration from 140 to 60 mM, but fell when NaCl concentration was further reduced. In contrast to orthograde perfusions it was insensitive to changes in flow rate. Our results are compatible with the thesis that feedback responses depend critically upon the rate of Cl- transport probably across the macula densa cells. Br- ions can replace Cl- because they appear to share a common transport pathway which can be inhibited with furosemide. Unspecificity of feedback responses during orthograde microperfusions is due to presence of Cl- ions in the macula densa region even when solutions are initially Cl- free. Cl- salts of divalent cations do not elicit a feedback response because Cl- transport is severely curtailed.

Animals↗
PubMed1976

Inter-relationship between autoregulation of glomerular filtration rate, tubuloglomerular feedback and juxtaglomerular renin activity in normotensive and hypertensive rats.

1. Reduction of renal perfusion pressure from 133 mmHg to 117 mmHg in control rats did not induce a significant change of kidney glomerular filtration rate (GFR) or nephron GFR determined in distal tubules. In contrast, nephron GFR measured in proximal tubular segments (NGFR-P) fell significantly. 2. Qualitatively the same response of filtration rate to changes of arterial blood pressure was found in the chronically clipped kidneys of Goldblatt hypertensive rats after acute removal of the clip. 3. In contrast, autoregulation of kidney GFR, NGFR-D and NGFR-P was abolished in the contralateral kidneys of Goldblatt hypertensive rats. 4. Microperfusion studies showed that tubuloglomerular feedback regulation of NGFR was present in the renin-rich ischaemic kidneys of Goldblatt rats after removal of the constricting clip, but greatly attenuated in the renin-depleted contralateral kidneys. 5. These data indicate that tubuloglomerular feedback participates in establishing renal autoregulation, possibly by mediation of the renin-angiotensin system.

Animals↗