Stop-flow Pressure Research Articles

The effect of 2 hours of complete unilateral ureteral obstruction on tubuloglomerular feedback control.

The mechanisms affecting renal blood flow and filtration during and after unilateral ureteral obstruction (UUO) are incompletely understood. Since ureteral obstruction leads to changes in interstitial pressure and volume, and since we have previously shown that interstitial pressure conditions can modulate the sensitivity of the tubuloglomerular feedback (TGF) control system, we sought in the present study to define the contribution of the TGF system to changes in GFR during and after UUO, and to observe associated changes in pressures in vessels, tubules and the interstitial space. Interstitial pressures and glomerular filtration rate (GFR) were measured in one group of Sprague Dawley rats. Interstitial hydraulic pressure was determined with a thin catheter placed in the subcapsular space. Interstitial oncotic pressure was estimated from the protein concentration in collected hilar lymph. In a second group of rats proximal tubule pressure (PT) and stop-flow pressure (PSF) were measured during the first three hours of UUO and after 24 h UUO. In a third group of rats PSF was measured while the loop of Henle was perfused at different rates. The sensitivity of the TGF system was determined from the maximal drop in stop-flow pressure (delta PSF) and the turning point (TP)--the tubule perfusion rate at which 50% of this maximal stop-flow pressure response was obtained. In a fourth group of rats proximal tubule flow-rate was measured after release of 2 hrs UUO. The results show that PT and PSF are both increased during the first three hours of obstruction and that they return to normal or sub-normal levels after 24 h of UUO.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of renal arterial angiotensin I infusion on glomerular dynamics in sodium replete dogs

During intrarenal infusion of angiotensin I (AI), conversion to angiotensin II (AII) within the kidney has been shown to occur early enough to decrease glomerular filtration rate (GFR). To evaluate further the mechanism by which AI decreases GFR, micropuncture studies were conducted in sodium replete dogs. Feedback-mediated alterations in glomerular function were minimized by reducing renal arterial pressure to 90 mm Hg. During infusion of AI (0.82 +/- 0.01 micrograms min-1), renal blood flow (3.91 +/- 0.25 ml min-1 g-1) and GFR (0.63 +/- 0.04 ml min-1 g-1) decreased by 36.7 +/- 6.1% and 18.9 +/- 6.1%, respectively. Similarly, single nephron GFR decreased from 66.4 +/- 3.8 to 40.0 +/- 3.2 nl min-1 and estimated glomerular plasma flow (280 +/- 49 nl min-1) decreased by 55 +/- 6%. Stop-flow pressure (40.5 +/- 3.6 mm Hg) did not change significantly, while proximal tubular (21.8 +/- 1.4 mm Hg) and peritubular capillary pressures (13.2 +/- 1.8 mm Hg) decreased by 25.5 +/- 2.8% and 49.4% +/- 5.1%, respectively. Glomerular capillary and effective filtration pressures were not altered significantly. There were increases in both preglomerular (168%) and efferent (203%) arteriolar resistances, along with a decrease in the glomerular filtration coefficient (Kf) from 4.6 +/- 0.6 to 2.5 +/- 0.5 nl mm Hg-1 min-1. These data indicate that augmented intrarenal conversion of circulating AI reduces GFR as a consequence of decreases in Kf as well as in glomerular plasma flow, the latter being due to concomitant increases in preglomerular and efferent arteriolar resistances.

Tubuloglomerular feedback and interstitial pressure in obstructive nephropathy

The possible role of the tubuloglomerular feedback (TGF) mechanism in the altered glomerular hemodynamics and tubular reabsorption which occur with prolonged (24-hr) ureteral obstruction and the changes in renal interstitial hydrostatic and oncotic pressure which may modulate TGF sensitivity were examined. The proximal tubule stop-flow pressure (PSF) response to increased distal tubular flow rates (TGF activity) was determined in rats with sham operation, 24-hr unilateral ureteral obstruction (UUO), or 24-hr bilateral ureteral obstruction (BUO), both before and for 2 hr after relief of obstruction. Subcapsular hydrostatic pressure, lymph flow and oncotic pressure, clearance and excretory data were measured in the second series of animals. During and after release of UUO, TGF sensitivity was increased, as indicated by the marked decrease in the loop perfusion rate at which 50% of the maximum decrease in PSF occurred (the turning point of TGF activation). Interstitial oncotic pressure but not hydrostatic pressure was significantly increased in UUO kidneys. In BUO rats, the turning point for TGF activation was slightly higher than the controls and the change in PSF with maximum loop perfusion rates was reduced, indicating a blunting of the TGF response before and particularly during postobstructive diuresis after release of BUO. Interstitial hydrostatic and oncotic pressures were both slightly increased resulting in no changes in net interstitial Starling forces. We conclude that enhanced TGF sensitivity after release of prolonged UUO, associated with increased interstitial oncotic pressure, may play a role in preventing postobstructive diuresis, while the blunting of TGF sensitivity after BUO may contribute to this phenomenon.

Pathophysiological changes in rat kidneys with partial ureteral obstruction since infancy

A partial ureteral obstruction (PUO) was created in 5-day-old rats by implanting the left ureter in the psoas muscle. The surgical technique was modified to produce mild or severe hydronephrosis [Hn (m) and Hn (s)]. The rats were studied at ages between 45 and 65 days with regard to kidney weight, number of functioning glomeruli, mean arterial blood pressure (MAP), total glomerular filtration rate (GFR), nephron filtration rate (SNGFR), tubular free-flow pressure (PT, and stop-flow pressure (SFP). Total GFR was determined after the release of obstruction. The other studies were performed in the obstructed state. Reference values were obtained from sham-operated and untouched control rats. The number of functioning nephrons was depressed 38% in Hn (m) and 73% in Hn (s). Total GFR was preserved in Hn (m) and depressed 54% in Hn (s). SNGFR in the remaining nephrons was significantly elevated in Hn (m) and normal in Hn (s). SFP was significantly elevated in Hn (s). The Hn (s) rats were hypertensive. The glomerular density was lower in the hydronephrotic than in the contralateral kidneys. This suggests a compensatory growth of the remaining nephrons in the Hn kidneys. We conclude that PUO present since infancy will either destroy the nephrons or elicit an adaptive response that will tend to preserve GFR.

The effect of intraarterial infusion of prostacyclin on the tubuloglomerular feedback control in the rat.

Effects of intraarterial prostacyclin (PGI2) infusions on interstitial hydrostatic and oncotic pressures and on the tubuloglomerular feedback (TGF) control of glomerular filtration rate (GFR) were studied in rat kidneys. The hilar lymph flow rate was used as a measure of interstitial hydrostatic pressure and the lymph protein concentration was used for interstitial oncotic pressure estimation. In the micropuncture experiments the stop-flow pressure technique was employed for determining the TGF characteristics, i.e. stop-flow pressure (PSF), maximal reduction of PSF (delta PSF) and turning point (TP), defined as the end-proximal flow rate at which 50% of delta PSF was obtained. Non-hypotensive doses of PGI2 (50 to 100 ng X kg-1 B.W. X min-1) infused in 30 min evoked an increase in urine and lymph flow rates and a decrease in lymph protein concentration, but did not affect GFR. delta PSF was reduced (9.9 +/- 1.0 mmHg versus 4.7 +/- 2.2 mmHg) and TP increased (22 +/- 2 nl/min versus 34 +/- 2 nl/min), but the PSF was unaffected. These changes were seen during the infusion period and during the immediate post-infusion control period of 30 min. Our data indicate that non-hypotensive doses of PGI2 in some way can affect the renal interstitial pressure and the TGF control system.

Effect of diuretics on the tubuloglomerular feedback response.

To study the influence of diuretics on the tubuloglomerular feedback mechanism, early proximal stop-flow pressure (SFP) was measured during loop exposure to different drug concentrations. SFP was recorded continuously during arrested flow and at a perfusion rate of 50 nL/min. The perfusate consisted of isotonic saline, to which varying amounts of furosemide. bumetanide, piretanide, or hydrochlorothiazide were added to obtain final concentrations between 10(-6) and 10(-4)M. The loop diuretics furosemide, bumetanide, and piretanide showed inhibition: an inverse log-linear relation between the luminal concentration and the respective feedback response. No differences between the dose-response curves of furosemide, bumetanide, or piretanide could be demonstrated. The effective concentration range was between 10(-6) and 10(-4)M, the mean effective dose (ED50) was close to 10(-5)M for each of them. In contrast, hydrochlorothiazide did not alter the feedback response. The effect of loop diuretics was rapidly and repeatedly reversible.

Extracellular fluid expansion and autoregulation in nephrotoxic serum nephritis in rats

Previous studies of the early autologous phase of bilateral nephrotoxic serum nephritis (NSN) in rats showed that whole kidney and single nephron glomerular filtration rate (GFR) were maintained at normal levels despite a 60% reduction in the product of surface area and hydraulic permeability (Kf). Factors responsible for this compensation were an increase of net ultrafiltration pressure, due primarily to an increased glomerular capillary pressure (PGC). This study was designed to investigate some possible causes of the compensation. Rats with bilateral NSN and normal GFR had an increased extracellular fluid volume (ECFV) 2 weeks after induction of NSN; control subjects did not change. To determine whether this ECFV expansion was responsible for triggering the compensation, we developed a unilateral NSN model with one diseased and one normal kidney. Unilaterally diseased rats did not experience an increase of ECFV. Values of Kf were 0.069 +/- 0.012 nl sec-1 mm Hg-1 in control subjects, 0.037 +/- 0.005 in bilateral NSN, and 0.043 +/- 0.006 in unilateral NSN. The elevation in PGC was the same in unilateral NSN as in bilateral NSN subjects and the same was true for the hydrostatic pressure difference across glomerular capillaries (delta P). Furthermore, in paired measurements on both kidneys of rats with unilateral NSN, PGC was significantly higher in the unilaterally diseased kidney than in the nondiseased kidney; sham control subjects had no difference. These results are interpreted to indicate that the signal that causes elevation of net ultrafiltration pressure is not a consequence of a systemic effect of NSN, but arises within the diseased kidney itself. To determine whether that signal involved some change in the mechanisms mediating autoregulation measurements were made of the response of whole kidney GFR and RBF to acute changes in arterial BP. Control rats and rats with NSN autoregulated both GFR and blood flow equally well. Tubuloglomerular feedback was studied by microperfusing loops of Henle and measuring proximal stop-flow pressure and early proximal flow rate. Stop-flow pressure was 4.0 mm Hg higher in rats with NSN at a loop perfusion rate of 10 nl/min, approximately the same difference that was found by direct measurement of PGC, but the sensitivity of response to changes in perfusion rate was the same in NSN as in control subjects. Finally, end proximal tubule flow rate was higher in NSN than in control subjects reflecting decreased proximal reabsorption. Thus, a normal feedback mechanism receives a signal that should cause afferent arteriolar constriction in NSN rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Kidney Function during Decreased Perfusion Pressure Due to Aortic Clamping and Hemorrhagic Hypotension: A Single Nephron Study in Dog Kidney

Whole kidney and single nephron function was compared in dogs during a stepwise lowering of renal perfusion pressure (PP) induced by aortic clamping (C) or hemorrhagic hypotension (HH). In C, renal vascular resistance (RVR) decreased with decreasing PP, the decrease being due to a drop in afferent resistance (RA) only. HH was associated with a rise in RVR due in the first phase mainly to an increase in RE, later to both RA and RE. There was a decrease in total kidney blood flow (RBF), glomerular filtration rate (GFR), glomerular and peritubular capillary pressure, and proximal tubular pressure. In C, RBF and GFR showed no significant difference at PPs 17 and 13 kPa. However, single nephron pressures were slightly but significantly lowered. In both groups, glomerular capillary hydraulic pressure (GCP) was significantly higher when calculated as SFP + piA (stop flow pressure + systemic arterial plasma oncotic pressure) than when measured directly by puncturing glomerular capillaries after ablation of a small layer of superficial cortex. This difference disappeared at PP 8 kPa. Ultrafiltration coefficient (Kf) seemed to increase with decreasing PP.

Effect of loop of Henle flow rate on glomerular capillary pressure.

Studies were performed in male Munich-Wistar rats weighing a mean of 100 g to evaluate further the hemodynamic effects of changing loop of Henle flow rate. When late proximal flow rate was varied by microperfusion from the late proximal tubule, single nephron glomerular filtration rate (SNGFR) measured in the early proximal tubule fell from 17.2 +/- 0.86 nl min-1 at a perfusion rate of zero to 11.8 +/- 0.88 nl min-1 at a perfusion rate of 14 nl min-1. Further increases in loop flow did not further depress SNGFR. Glomerular capillary pressure (Pgc) was measured directly in superficial glomeruli while loop of Henle flow was varied. Elevating loop flow was followed by a rapid decrease in Pgc, which was reversible when flow was reduced. The mean response to maximum stimulation was a decrease in Pgc of 6.6 +/- 0.7 mm Hg, and the response was close to maximum at a perfusion rate of 14 nl min-1. Parallel changes in stop-flow pressure were observed. These findings, together with previous observations that increasing loop of Henle flow results in decreased single nephron blood flow, permit the conclusion that the dominant vascular response to elevated loop of Henle flow is constriction of the afferent arteriole.

Indomethacin inhibits renal functional adaptation to nephron loss.

Immediately after unilateral nephrectomy, the glomerular filtration rate (GFR) and urinary excretion rate increase in the remaining transplanted rat kidney. In a previous study, we found that GFR in a transplanted kidney was reduced through an activation of the tubuloglomerular feedback control. Excision of the rat's own remnant kidney then reduced feedback sensitivity and thereby allowed GFR to rise. The present study aimed at investigating whether prostaglandins are involved in this functional adaptation. Clearance and micropuncture experiments were performed before and after administration of indomethacin and after subsequent unilateral nephrectomy. GFR and the urinary excretion rate of electrolytes and water were measured. From proximal tubular stop-flow pressure (PSF) measurements the feedback characteristics were determined as the maximal stop-flow pressure response (delta PSF) to an increase in distal flow and the turning point (TP), i.e. the end proximal flow rate that caused 50% reduction of delta PSF. The results showed that following nephrectomy the tubuloglomerular feedback sensitivity was decreased, with an increased TP and reduced delta PSF. Pretreatment with indomethacin (2 mg/kg BW) prevented not only the change in feedback sensitivity at nephrectomy but also the rise in GFR. These results suggest that the prostaglandins play a possible role as one link in the chain of adaptive events occurring immediately after nephron loss.

Glomerular hemodynamics in persistent renovascular hypertension in the rat.

We studied the glomerular hemodynamics and activity of the tubuloglomerular feedback system (TGFS) in Wistar rats with persistent hypertension 60 days after removal of the clipped kidney in the Goldblatt (two-kidney, one clip) hypertension model. Ten hypertensive rats (HBP) were compared with 12 normotensive ones (NBP). Micropuncture studies revealed that values for the single nephron glomerular filtration rate (SNGFR), glomerular plasma flow (QA), and afferent oncotic pressure (PAR.A) were similar in both groups, whereas glomerular capillary pressure (PGC) and effective filtration pressure (EFP) were higher in the HBP group (p less than 0.05). A slight but insignificant increase in afferent resistance was present in the HBP group. A positive correlation was found between mean arterial pressure and stop flow pressure (SFP) (r = 0.64, p less than 0.05) but not with SNGFR, suggesting a reduction in the ultrafiltration coefficient in hypertensive rats. This was further supported by studies of the activity of the TGFS, which demonstrated that interrupting flow to the macula densa was followed by a smaller increment in SNGFR in HBP, in spite of a similar rise in SFP. The mechanism responsible for decreasing glomerular permeability is unknown but could be related to structural changes in glomerular capillary or to an increase in intrarenal angiotensin II, as has been demonstrated previously in this model. It is suggested that these adaptations occurring in the kidney exposed to hypertension can contribute to the maintenance of elevated arterial pressure after removing the stenotic kidney.

The effect of tubular perfusion with PGE2, PGF2 alpha, and PGI2 on the tubuloglomerular feedback control in the rat.

The prostaglandins (PG) of the renal medulla might affect the nephron and the cortical arteriolar function via the tubular route. To investigate this question PGE2 (1 microgram/mL), PGF2 alpha (10 micrograms/mL), or PGI2 (1 ng/mL) was added to the tubular perfusion solution when the characteristics of the tubuloglomerular feedback (TGF) control were measured. The experiments were performed on Sprague-Dawley rats. The proximal tubular stop-flow pressure (PSF) was measured upstream to a wax block, while at the same time the distal nephron was perfused with prostaglandin-containing or prostaglandin-free solutions at different flow rates varying from 0 to 50 nL/min. The maximal drop in PSF (delta PSF) and the tubular flow rate at which 50% of the delta PSF response was obtained, the turning point (TP), were determined. When PGE2 or PGF2 alpha was added to the tubular perfusion solution in the control animals a significant increase in feedback sensitivity was found. After 10 min of tubular PGI2 perfusion the feedback sensitivity was almost completely abolished, with a delta PSF of 0.8 mmHg (1 mmHg = 133.322 Pa) (control 8.4 mmHg) and a TP of greater than 40 nL/min (control 22 nL/min). After nephrectomy the feedback sensitivity was reduced, with a delta PSF of 2.0 mmHg and a TP of greater than 40 nL/min. When PGE2 was added to the tubular perfusion solution in the uninephrectomized animals, the feedback sensitivity was increased to the control level, with a delta PSF of 8.2 mmHg and a TP of 20.0 nL/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of renal tubular obstruction on stop-flow pressure and glomerular deposition of fibrin during intravascular coagulation in the rat

Intravascular coagulation in the rat kidney was induced by intravenous infusion of thrombin for 1 hr. The proximal tubular free-flow (Pt) and stop-flow (Psf) pressures were measured by micropuncture. Some proximal tubules were obstructed with solid paraffin before infusion of thrombin. In certain rats saralasin or indomethacin was administered for 1 hr starting 30 min after the thrombin infusion, and the effect on the tubular pressures was studied. The deposition of fibrin in the glomeruli was examined by light and electron microscopy. Pt fell from 15 +/- 1 (SE) to 7 +/- 2 mm Hg (P less than 0.05) during the infusion of thrombin. After a brief period of increased pressure the Psf fell rapidly from 37 +/- 1 to 17 +/- 1 mm Hg (P less than 0.05). In the previously obstructed nephrons the pressure (Po) increased parallel to the increase in Psf but remained elevated after the infusion of thrombin, 54 +/- 2 mm Hg. The arterial blood pressure (Pa) increased from 119 +/- 2 to 138 +/- 3 mm Hg (P less than 0.05). Saralasin raised the Psf from 15 +/- 1 to 19 +/- 1 mm Hg (P less than 0.05) but had no effect on Pt, Po, or Pa. Indomethacin did not influence the pressures. Morphological examination revealed fibrin in all glomeruli of normal nephrons. In the previously obstructed nephrons the deposition of fibrin was almost totally prevented. The results suggest that glomerular filtration is important for deposition of fibrin in the kidney.

Effects on renal hemodynamics of intra-arterial infusions of angiotensins I and II.

Experiments were conducted in anesthetized dogs to evaluate the differences between the effects of intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) and those of circulating ANG II on renal blood flow (RBF), glomerular filtration rate (GFR), peritubular capillary pressure (PCP), proximal tubular free-flow pressure (PTP), and stop-flow pressure (SFP). Equiconstrictor doses of ANG I and ANG II were infused into the renal arteries of dogs kept on normal and high sodium diets. In clearance experiments, RBF decreased by 23% (low dose) and 33% (high dose) during the infusion of either ANG I or ANG II; GFR was significantly reduced only during the ANG I infusion. In micropuncture experiments, in which the GFR responses were similar, there were significant reductions in PTP (23 +/- 3%) and PCP (33 +/- 3%) during the intrarenal ANG I infusion; SFP was not altered significantly. Afferent and efferent arteriolar resistances increased significantly during ANG I infusion as well as during infusion of ANG II. These results indicate that during intra-arterial infusion of ANG I, the conversion to ANG II within the kidney occurs early enough to decrease glomerular filtration rate through an apparent increase in preglomerular resistance.

Renal hemodynamic actions of angiotensin II: interaction with tubuloglomerular feedback.

The present study was designed to investigate the importance of interactions between angiotensin II (ANG II) and other intrinsic control mechanisms, including tubuloglomerular feedback (TGF), in controlling renal hemodynamics. When endogenous ANG II formation was blocked by SQ 14225 infusion and changes in myogenic activity were minimized by servo controlling renal arterial pressure, ANG II infusion (20 ng . kg-1 . min-1 iv) did not change glomerular filtration rate but decreased renal blood flow (RBF) from 286 +/- 36 to 179 +/- 31 ml/min due to increases in calculated preglomerular (54%) and efferent (100%) arteriolar resistances. After inhibition of TGF by occluding the ureter during mannitol diuresis, ANG II infusion (20 ng . kg-1 . min-1) decreased RBF from 229 +/- 25 to 151 +/- 19 ml/min while increasing glomerular hydrostatic pressure (calculated from ureteral stop-flow pressure and plasma colloid osmotic pressure) from 56.7 +/- 2.5 to 62.3 +/- 2.2 mmHg. Postglomerular resistance increased to 173 +/- 17% of control, but preglomerular resistance did not change significantly during ANG II infusion after inhibition of TGF. These data suggest that the direct renal vasoconstrictor action of ANG II is confined mainly to postglomerular vessels and that changes in preglomerular resistance that occur when ANG II levels are inappropriately elevated in normal animals are caused by other intrinsic control mechanisms, such as TGF.

Prevention of ischemic acute renal failure with impermeant solutes.

Studies were performed to evaluate the effect of solute permeability and extracellular osmolality in protecting against ischemic acute renal failure. The functional protective effect of a 1-min intrarenal perfusion (prior to intrarenal norepinephrine 0.75 micrograms . kg-1 . min-1) of a hypertonic permeant solute (hypertonic saline, 1,400 mosmol/kg H2O) and an isotonic impermeant solute (isotonic mannitol, 280 mosmol/kg H2O or isotonic polyethylene glycol, IPEG, 300 mosmol/kg H2O) was evaluated. Three hours after ischemia, the glomerular filtration rate was significantly lower in hypertonic saline group vs. either the isotonic mannitol- or IPEG-treated animals (2.4 vs. 8.9 and 10.4 ml/min, respectively; both P less than 0.05). Mean renal blood flow was similar in all three groups. The effects of hypertonic saline and IPEG on glomerular filtration pressure and tubular obstruction were also evaluated. Stop-flow pressure, as an index of glomerular filtration pressure, was higher in the IPEG- vs. the hypertonic saline-treated animals (40 vs. 35 mmHg, P less than 0.001). Although proximal tubular pressure was increased in both groups, transglomerular hydrostatic pressure was higher in the IPEG vs. the hypertonic saline group (13 vs. 6 mmHg, P less than 0.01). Tubular microperfusion studies demonstrated increases in proximal tubular pressure in the hypertonic saline but not the IPEG studies. The present results indicate that isotonic, impermeant solutes provide functional protection against ischemic acute renal failure. The beneficial effect of impermeant solute is mediated, at least in part, by better maintenance of transglomerular hydrostatic pressure and prevention of secondary tubular obstruction.

Evidence for tubuloglomerular feedback in juxtamedullary nephrons of young rats.

To determine whether the filtration rate of juxtamedullary nephrons is regulated by tubuloglomerular feedback (TGF), we developed two micropuncture techniques suitable for the papilla of young rats. One consisted of measuring the tubular flow in descending limbs of Henle loops (VDLH) while the ascending limbs of the loop of Henle (ALH) were perfused at various rates with three different solutions: modified Ringer, artificial Henle loop solution, and Ringer containing 10(-4) M furosemide. SNGFR was also measured in several juxtamedullary nephrons. The other protocol consisted of measuring the tubular stop-flow pressure (PSF) in descending limbs of the loop of Henle upstream to a wax block. Distal to the block Ringer was perfused at various rates through ALH. Our results provide the first evidence of a TGF response in juxtamedullary nephrons. VDLH and SNGFR decreased during Ringer perfusion to 42 +/- 4 and 44 +/- 4% of their values at zero perfusion. The same pattern was observed using Henle loop solution as perfusate, whereas with furosemide VDLH did not change. The maximal decrease in PSF was 14.1 +/- 1.4 mmHg. The perfusion rate necessary to induce a half-maximal PSF decrease was 9.1 +/- 0.9 nl/min. Similar micropuncture techniques were used in proximal tubules of surface nephrons in these rats, which in comparison to the deep nephrons showed smaller feedback responses. The mechanism seems to be active at physiological nephron flow rates in both nephron populations. Thus, TGF can exert its effect on GFR of the whole kidney by acting in both deep and surface nephrons.

A new method for estimating intestinal capillary pressure.

The purpose of this study was to compare the venous occlusion method for measuring capillary pressure with the stop-flow isovolumetric method in the cat small intestine. Venous occlusion pressures were determined from the inflection point of the venous pressure tracing after sudden occlusion of the venous outflow cannula. Venous occlusion pressure was highly correlated (r = 0.98, P less than 0.01) with stop-flow capillary pressure. This finding indicates that the major sites of fluid filtration and vascular capacitance reside at the same segment of the intestinal microcirculation. The venous occlusion method is a relatively simple technique for measuring whole-organ capillary pressure that is not constrained by the technical difficulties associated with volumetric/gravimetric techniques.

Activation of the tubuloglomerular feedback mechanism in dehydrated rats.

To study the influence of the tubuloglomerular feedback control (TGF) on the regulation of glomerular filtration rate (GFR) during dehydration, micropuncture experiments were performed on surface nephrons of dehydrated rats. Dehydration was achieved by withdrawal of food and water for 24 h. The urine flow rate decreased to 1.5 microliters/min (controls 2.9 microliters/min) and GFR decreased in these rats to 0.80 ml/min (controls 1.22). TGF was studied by two different micropuncture procedures. With the first technique the changes in proximal stop-flow pressure in response to changes of the late proximal microperfusion rate were measured. With this technique the perfusion rate necessary to induce a half maximal stop-flow pressure response, the turning point, was also determined. An increased TGF sensitivity was found in dehydrated rats, as indicated by increased stop-flow pressure responses (35 versus 26%) and decreased turning points (16 versus 21 nl/min). With the second micropuncture technique the single nephron GFR (SNGFR) was measured at distal and proximal tubular sites, in the same nephron. Distal SNGFR was decreased during dehydration to 32.2 nl/min, versus 42.7 nl/min in controls. A significant difference between paired SNGFR measurements in the same nephron was observed during dehydration, the proximal value being 5.3 nl/min higher than the distal, whereas this difference was not seen in control rats. This finding indicates that activation of the feedback mechanism takes place to reduce SNGFR. It is concluded that the decrease in whole kidney GFR is partly caused by the observed increase in feedback activity. The present results are also in agreement with our earlier hypothesis that the hydrostatic and oncotic pressure conditions within the interstitial space surrounding the macula densa cells modulate the sensitivity of the tubuloglomerular feedback mechanism.

The role of tubuloglomerular feedback in acute impairment of renal function in obstructive jaundice.

Acute renal functional impairment not infrequently accompanies liver dysfunction and, particularly with bile duct obstruction, may be extremely severe. Recent studies suggest that tubuloglomerular feedback (TGF) activated by circulating non-electrolyte factors which occur during liver dysfunction may contribute to the intense renal vasoconstriction thought to be central to the functional renal impairment. In this study, serum from two patients with obstructive jaundice (OJ) and renal impairment, and from rats with OJ due to bile duct ligation were either dialysed or treated with furosemide, known to block electrolyte-mediated TGF. These sera, when perfused into loops of Henle in rat nephrons, induced a significant fall of 28% in stop-flow pressure, an indirect measure of glomerular capillary pressure thus implying arteriolar vasoconstriction. These findings are consistent with the hypothesis that circulating, non-electrolyte factors, which stimulate TGF, occur in cases of obstructive jaundice and that these may contribute to the renal impairment.