Fluid Reabsorption In Proximal Tubule Research Articles

Acute effects of gentamicin on thick ascending limb function in the rat

It is well established that the aminoglycoside antibiotics can adversely affect proximal tubule function. Predominantly indirect evidence suggests that aminoglycosides may also affect function of more distal nephron segments. The present study utilized whole kidney clearance, in vivo micropuncture and in vitro microperfusion to directly determine whether acute gentamicin treatment affects sodium chloride transport in the thick ascending limb of the loop of Henle. Gentamicin (25 mg/kg) significantly increased urine flow, as well as sodium, potassium and chloride excretion within 15 min of intravenous injection. Glomerular filtration rate and proximal tubule fluid reabsorption were not altered by acute gentamicin treatment. In contrast, both fractional and absolute loop chloride transport was significantly decreased. In the in vitro microperfused medullary thick ascending limb, luminal but not basolateral administration of gentamicin (1 mM) significantly decreased chloride reabsorption when compared to time controls. These data suggest that the increased urine and electrolyte excretion associated with acute gentamicin treatment is, at least in part, a consequence of decreased transport in the thick ascending limb of Henle's loop.

Model of TGF-proximal tubule interactions in renal autoregulation

Previous models, assuming constant reabsorption in the proximal tubule, have shown that tubuloglomerular feedback (TGF) can explain only a fraction of glomerular filtration rate (GFR) and renal blood flow autoregulation. Increased arterial pressure inhibits proximal tubule fluid reabsorption, an effect that should increase the efficacy of TGF because of the resulting increased flow rate in the loop of Henle. Models describing pressure and flow in a glomerulus and a nephron were derived to test this prediction. The models were coupled by a TGF function with tubular flow rate at the end of the proximal tubule (superficial nephron) or at the macula densa (juxtamedullary nephron) as input and with afferent arteriolar resistance as output. In agreement with others, the model predicted that TGF alone could account for about one-half of autoregulation. Pressure-dependent inhibition of proximal reabsorption increased the ability of TGF to account for autoregulation, providing compensation for increases in arterial pressure comparable to published whole kidney values. The inclusion of an approximation of an effect of arterial pressure on TGF marginally improved predicted autoregulation. Although the results suggest that the proximal tubule-TGF interaction can provide a quantitatively adequate explanation for autoregulation, they also indicate that the effect of the interaction is spent at arterial pressures greater than 130 mmHg. Additional mechanisms are required to extend this range.

Persistent proximal tubule dysfunction late in Heymann nephritis

To determine whether proximal tubule function returned to normal after cessation of active immunological injury in Heymann nephritis, we compared kidney function in an acute stage of the disease, when antibodies were being deposited on the brush border, to a later, chronic stage. Renal blood flow measurements via a flow probe, along with clearance and micropuncture techniques, were used to measure renal plasma flow, glomerular filtration rate, protein and albumin excretion, organic ion (PAH and TEA) extraction and tubule fluid inulin concentration. Proximal tubule fluid reabsorption, which was depressed in the acute stage of injury, returned to normal in chronic Heymann nephritis, but both PAH and TEA extraction continued to be depressed. PAH extraction was also decreased in isolated perfused kidneys from rats with Heymann nephritis. A three fold increase in PAH content of these perfused kidneys indicated that there was a defect in luminal PAH transport. Reconstitution of the proximal tubule brush border in chronic Heymann nephritis was not accompanied by functional recovery of secretory processes.

Altered responsiveness of proximal tubule fluid reabsorption of peritubular angiotensin II in spontaneously hypertensive rats

Stimulation of proximal tubular fluid reabsorption by peritubular angiotensin II (Ang II) was examined by split-drop micropuncture in 5- and 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). In WKY, the maximum stimulation occurred at 10(-11) mol/l and the response did not vary with age. In 5-week-old SHR, the dose-response relationship was similar in shape and in the extent of the maximum response but was shifted one half-logarithmic step to the right, indicating decreased sensitivity to Ang II. In contrast, the dose-response relationship was shifted one half-logarithmic step to the left in 12-week-old SHR compared with WKY. Alterations in the responsiveness of the proximal tubule to Ang II in young SHR could contribute to sodium retention observed during development of hypertension in these rats.

The effect of loop diuretics on fluid reabsorption from the rat proximal convoluted tubule

The effects of the 'loop diuretics' bumetanide, furosemide and piretanide on fluid reabsorption from the rat proximal convoluted tubule have been tested to assess whether a Na(+)-Cl- cotransport mechanism can support fluid reabsorption from this nephron segment. Proximal convoluted tubules were perfused in vivo at 25 nl min-1 with chloride Ringer solutions containing [3H]inulin. Fluid reabsorptive rate (Jv) was 2.05 +/- 0.07 nl mm-1 min-1 (n = 115) from control chloride Ringer. Bumetanide at 10(-6) and 10(-5) M reduced Jv by about 40%. Bumetanide at 10(-7) M, furosemide (10(-4) and 10(-5) M) and piretanide (10(-4) and 10(-5) M) had no effect on Jv. At 10(-3) M, furosemide and piretanide reduced Jv by about 45%. The results show that luminal application of loop diuretics lowers fluid reabsorption from the proximal convoluted tubule and the order of potency for inhibiting reabsorption is bumetanide greater than furosemide identical to piretanide. The specificity of the loop diuretics at their effective concentrations needs to be confirmed, however, before attribution of a role for Na(+)-Cl- co-transport in the support of proximal tubule fluid reabsorption.

Insulin increases loop segment chloride reabsorption in the euglycemic rat.

To elucidate the nephron segment(s) responsible for insulin's antinatriuretic effect in the mammalian kidney, late proximal, early distal, and late distal tubule micropuncture was performed during base-line and intravenous insulin infusion in glucose-clamped, volume-expanded rats. During insulin infusion, urinary sodium chloride excretion fell. Blood glucose, arterial pressure, whole kidney and single-nephron inulin clearance, fluid, and chloride delivery out of the proximal convoluted tubule remained unchanged. Early distal chloride delivery decreased (P less than 0.001) during insulin administration. Insulin infusion increased calculated loop chloride reabsorption compared with both base-line values and values for time-control rats. Distal convoluted tubule chloride reabsorption was unchanged during insulin administration. We conclude that 1) euglycemic insulin administration reduces urinary chloride excretion in volume-expanded rats by tubular mechanisms; 2) in superficial nephrons, insulin has no effect on proximal tubule fluid or chloride reabsorption but markedly stimulates chloride reabsorption in the loop; and 3) chloride reabsorption in the distal convoluted tubule was unaltered by insulin administration.

Age-related changes in angiotensin II-stimulated proximal tubule fluid reabsorption in the spontaneously hypertensive rat.

The development of hypertension in the spontaneously hypertensive rat (SHR) up to 8 weeks of age involves sodium retention with reduced fractional sodium excretion. Since angiotensin II (Ang II) directly stimulates proximal tubular sodium transport, we investigated age-related changes in proximal reabsorption (Jv), using shrinking split-drop micropuncture before and after enalaprilat in SHR at 5, 7 and 12 weeks of age and in age-matched Wistar-Kyoto rats (WKY). Control values for Jv were higher in the SHR than in WKY at 5 weeks, but lower at 7 and 12 weeks, consistent with an early phase of sodium retention. Enalaprilat reduced mean Jv by approximately 15% in all WKY groups, indicating the extent of Ang II-stimulated transport. In the SHR there was an age-dependent reduction in the effect of enalaprilat on Jv, and by 12 weeks no Ang II stimulation could be detected. Age-related changes in proximal tubular reabsorption could contribute to sodium retention in the young SHR and may reflect a more general pattern of inherited transport defects.

Time course of proximal tubule response to acute arterial hypertension in the rat.

Acute hypertension was previously shown to cause partial inhibition of proximal tubule fluid reabsorption in perfused tubules in the rat. If the inhibition also occurs in unobstructed tubules receiving native glomerular filtrate, hypertension should increase end proximal flow rate despite autoregulation of glomerular filtration rate (GFR). We tested this prediction with a videodensitometric method recently developed for measurement of tubular flow rate that does not interrupt flow to the macula densa. Hypertension was induced by increasing total peripheral resistance in rats receiving several hormones at rates designed to maintain high levels of these agents. End proximal flow rate was increased 18% as early as 1.5-2 min following the induction of hypertension and increased over the course of the next 25-30 min to reach values 50% greater than controls as the hypertension was sustained. Whole-kidney GFR and renal blood flow were fully autoregulated. The results confirm that hypertension increases the fluid load to the loop of Henle, and are consistent with an effect on proximal tubule fluid reabsorption. This increase in fluid load could signal the macula densa and contribute to the efficacy of autoregulation; it could also provide a significant fraction of the increased fluid and salt excretion of pressure natriuresis.

Regulation of ammonia production by mouse proximal tubules perfused in vitro. Effect of luminal perfusion.

To investigate factors regulating ammonia (NH3) production by isolated defined proximal tubule segments, we examined the rates of total NH3 (NH3 + NH+4) production by individual proximal tubule segments perfused in vitro under a variety of perfusion conditions. Segments consisting of late convoluted and early straight portions of superficial proximal tubules were incubated at 37 degrees C in Krebs-Ringer bicarbonate (KRB) buffer containing 0.5 mM L-glutamine and 1.0 mM sodium acetate, pH 7.4. The rate of total ammonia production was calculated from the rate of accumulation of total NH3 in the bath. The total ammonia production rate by unperfused proximal segments was 6.0 +/- 0.2 (+/- SE) pmol/mm per minute, which was significantly lower than segments perfused at a flow rate of 22.7 +/- 3.4 nl/min with KRB buffer (21.5 +/- 1.4 pmol/mm per minute; P less than 0.001) or with KRB buffer containing 0.5 mM L-glutamine (31.9 +/- 2.5; P less than 0.001). The rate of NH3 production was higher in segments perfused with glutamine than in segments perfused without glutamine (P less than 0.01). The perfusion-associated stimulation of NH3 production was characterized further. Analysis of collected luminal fluid samples revealed that the luminal fluid total NH3 leaving the distal end of the perfused proximal segment accounted for 91% of the increment in NH3 production observed with perfusion. Increasing the perfusion flow rate from 3.7 +/- 0.1 to 22.7 +/- 3.4 nl/min by raising the perfusion pressure resulted in an increased rate of total NH3 production in the presence or absence of perfusate glutamine (mean rise in rate of total NH3 production was 14.9 +/- 3.7 pmol/mm per minute in segments perfused with glutamine and 7.8 +/- 0.9 in those perfused without glutamine). In addition, increasing the perfusion flow rate at a constant perfusion pressure increased the rate of luminal output of NH3. Total NH3 production was not affected by reducing perfusate sodium concentration to 25 mM and adding 1.0 mM amiloride to the perfusate, a condition that was shown to inhibit proximal tubule fluid reabsorption. These observations demonstrate that the rate of total NH3 production by the mouse proximal tubule is accelerated by perfusion of the lumen of the segment, by the presence of glutamine in the perfusate, and by increased perfusion flow rates. The increased rate of NH3 production with perfusion seems not to depend upon normal rates of sodium reabsorption. The mechanism underlying the stimulation of NH3 production by luminal flow is unknown and requires further study.

Short term effect of low doses of tri-iodothyronine on proximal tubular membrane Na−K-ATPase and potassium permeability in thyroidectomized rats

Tri-iodothyronine (T3), even when administered for short time and at low doses, induces a large increase in the isotonic fluid reabsorption (Jv) in proximal tubules of thyroidectomized rats (TX). In order to investigate the role of the Na-K-ATPase in this process, we measured the Na-K-ATPase activity in early proximal convoluted tubules (S1) and proximal straight tubules (S2) microdissected from TX rats and rats treated with low doses of T3 (10 micrograms/kg body wt), either for 3 days (TX + 3T3) or for 7 days (TX + 7T3). In both segments no changes in Na-K-ATPase activity were found in TX + 3T3 rats versus TX rats, while an increase was registered in TX + 7T3 rats. Using micropuncture techniques, Jv measured on the same tubular segments increased by 68% in TX + 3T3 rats versus TX. Thus, no correlation between Jv and Na-K-ATPase activity measured in vitro could be detected after short term treatment of TX rats with T3. Na-K-ATPase activity in vivo is also regulated by the potassium permeability of the membrane, which might be altered by tri-iodothyronine. This hypothesis was tested by perfusing intraluminally and peritubularly proximal tubules of TX rats with the K ionophore, valinomycin (1 microgram/ml). In the dual perfusion experiments valinomycin elicited 40% of the action induced on Jv by 3 days treatment with T3. On the other hand, no further increase in Jv was recorded when valinomycin was applied in TX rats pretreated with T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Effector loci for renal nerve control of cortical microcirculation.

To determine the effector loci for renal neural vasomotor control, we performed micropuncture measurements before or after renal nerve stimulation and during low- (0.5-1.5 Hz) (LFS) or high- (3-5 Hz) (HFS) frequency nerve stimulation in Munich-Wistar rats. In response to HFS, single nephron glomerular filtration rate decreased on average from 24.1 +/- 4.1 to 10.4 +/- 2.3 nl/min. Although mean glomerular transcapillary hydraulic pressure difference remained essentially constant, HFS led to a marked fall in glomerular plasma flow rate (71.3 +/- 0.9 to 44.1 +/- 10.4 nl/min). The latter was associated with significant increase in both afferent (RA) and efferent (RE) arteriolar resistance, on average by more than twofold. Because of this profound arteriolar constriction, early peritubular capillary hydraulic pressure (PEA) fell markedly during HFS (mean: 19.1 +/- 1.4 vs. 13.2 +/- 1.4 mmHg). The ultrafiltration coefficient (Kf) also decreased significantly, on average from 0.055 +/- 0.014 to 0.015 +/- 0.002 nl/(s . mmHg) with HFS. By contrast, LFS affected these indices to a much lesser and more variable degree although the marked decline in PEA was again demonstrated. Despite this decrease in postglomerular capillary hydraulic pressure, absolute proximal tubule fluid reabsorption (APR) failed to change in some animals and decreased slightly in others. Analysis of the Starling forces acting across the peritubular capillaries showed that due largely to a uniform decrease in mean peritubular capillary hydraulic pressure, mean net reabsorption pressure (Pr) rose substantially and significantly, on average by more than 5 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lysine on bicarbonate and fluid absorption in the rat proximal tubule.

The effects of lysine on bicarbonate and fluid reabsorption in the rat proximal tubule were studied by luminal and capillary perfusion in situ. The proximal tubule and peritubular capillaries were perfused with bicarbonate Ringer solution containing [14C]inulin. The rate of bicarbonate reabsorption (JHCO3) was estimated to be 124 +/- 9.5 peq.min-1.mm-1 using a pH membrane glass electrode. The rate of net fluid reabsorption (Jv) was 2.6 +/- 0.21 nl.min-1.mm-1. When 10 mM L-lysine was added to the luminal perfusate, a 35% reduction in JHCO3 and no change in Jv were observed. Increase of L-lysine concentration in the luminal perfusate to 20 mM did not reduce JHCO3 further nor did it influence Jv.l When 10 mM L-lysine was added to the capillary perfusate, a 13% reduction in JHCO3 was observed (NS). Increase of lysine concentration in the capillary perfusate to 20 mM significantly reduced JHCO3 by 26% (P less than 0.01). There was no significant change in Jv under both conditions. The effect of L-lysine in the lumen was related to its reabsorption kinetics, D-Lysine, which was not reabsorbed significantly, did not affect bicarbonate reabsorption in the proximal tubule. These results indicate that the inhibitory effect of L-lysine is related to the entry of lysine into the cell from the lumen.

Arachidonic acid metabolism, prostaglandins and the kidney

Renal prostaglandins are gaining increasing recognition as important modulators of hemodynamics and excretory function in the mammalian kidney. Synthesis of these unsaturated fatty acids from arachidonate precursors is closely regulated by intrarenal factors, and circulating angiotensin II, catecholamines, arginine vasopressin and bradykinin. Endogenous prostaglandins exert little influence on renal blood flow and glomerular filtration rate in the basal state, but inhibition of arachidonate metabolism when renal perfusion is impaired causes marked alterations in these parameters. Renal salt and water excretion is modified by the effects of prostaglandins on glomerular filtration rate, proximal tubule fluid reabsorption, medullary solute gradients, and the intrinsic water and ion reabsorptive properties of distal nephron segments. Prostaglandins also mediate renin release under basal conditions and in response to intravascular volume depletion. Abnormalities of renal prostaglandins are evident in various clinical disorders of renal function including hypertension, ureteral obstruction, Bartter syndrome, hypokalemic nephropathy and drug-induced disorders of water metabolism. Appropriate clinical use of nonsteroidal anti-inflammatory agents requires consideration of the potential renal consequences of inhibiting prostaglandin biosynthesis.

Effects of sodium orthovanadate on whole kidney and single nephron function

The renal effects of sodium vanadate (Na3VO4), an inhibitor of sodium-potassium-ATPase recently shown to be a potent diuretic, were studied by using clearance and micropuncture techniques in nondiuretic anesthetized rats. Administration of 1.0 mumole of sodium vanadate (high dose) increased urine flow rate (V) from 9.8 +/- 1.4 to 17.5 +/- 4.0 microliter/min (mean +/- SEM, P < 0.025), UNaF from 1.73 +/- 0.36 to 3.05 +/- 0.65 microEq/min (P < 0.025), and FENa from 0.67 +/- 0.15 to 1.24 +/- 0.28% (P < 0.025)., No significant changes in GFR or RPF were observed. Late proximal tubular-fluid-to-plasma (F/P) inulin decreased from 2.28 +/- 0.19 to a minimum value of 1.38 +/- 0.06 (P < 0.025). Absolute water reabsorption decreased from 15.8 +/- 3.5 to 6.5 +/- 1.7 nl/min (P < 0.025) and fractional water reabsorption from 52.0 +/- 4.4 to 26.5 +/- 4.1% (P < 0.025). The injection of 0.5 mumole of sodium vanadate (low dose) resulted in no significant changes in V. Late proximal F/P inulin decreased, however, from 2.37 +/- 0.14 to a minimum value of 1.59 +/- 0.12 (P < 0.025). SNGFR remained unchanged, as did GFR and RPF. UNaV increased from 1.41 +/- 0.35 to 2.25 +/- 0.35 microEq/min (P < 0.025), and FENa rose from 0.64 +/- 0.16 to 0.91 +/- 0.15% (P < 0.025). The decrease in F/P inulin was observed in all but one animal, even in the absence of a diuretic response. The amount of fluid remaining in the lumen of the late proximal tubule was virtually the same in both low- and high-dose animals (18.9 +/- 3.0 and 19.5 +/- 3.4 nl/min, respectively). We conclude that sodium vanadate causes a decrease in superficial proximal tubule fluid and salt reabsorption. Inasmuch as the low dose does not result necessarily in a diuretic response, an increase in fluid reabsorption distal to the late proximal tubule must take place.

Isolated nephron segments in a rabbit model of ischemic acute renal failure.

Renal artery occlusion has been extensively used in animal models to cause acute renal failure. The present isolated tubule microperfusion studies were designed to examine the transport characteristics of multiple nephron segments of the rabbit after 60 min of total renal ischemia. Preliminary studies showed that this maneuver produced significant and persistent elevations of serum creatinine. The tubules were perfused and bathed with artificial solutions simulating ultrafiltrate and studied at 37 degrees C. Four nephron segments were examined. Ischemia reduced proximal convoluted tubule fluid reabsorption 77% (0.72 +/- 0.11 vs. 0.14 +/- 0.06 nl . mm-1 . min-1, P less than 0.01) and cortical proximal straight tubule fluid reabsorption 88% (0.54 +/- 0.10 vs. 0.06 +/- 0.03 nl . mm-1 . min-1, P less than 0.005). Ischemia reduced the ability of the thick ascending limb of Henle's loop to lower perfusate chloride ion concentration 60% (-47 +/- 9 vs. -19 +/- 3 meq/liter, P less than 0.02) and its diluting ability 49% (-87 +/- 15 vs. -44 +/- 7 mosmol/kg H2O, P less than 0.01). Ischemia reduced the antidiuretic hormone-dependent osmotic water permeability of the cortical collecting tubule 59% (0.0203 +/- vs. 0.0083 +/- 0.0020 cm/s, P less than 0.01). Morphologic alterations were noted in the proximal segments but not in the distal segments of the nephron. The current studies demonstrate that 60 min of renal ischemia impairs the transport capability of all proximal and distal nephron segments studied.

Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat.

Micropuncture study was performed in 21 mildly volume-expanded Munich-Wistar rats before and during partial aortic constriction to examine the effects of endogenous prostaglandins (PG) and angiotensin II (AII) on single nephron glomerular filtration rate (SNGFR) and absolute proximal reabsorption rate (APR). Animals received either vehicle (group 1), indomethacin (group 2), or indomethacin plus saralasin (group 3). Before aortic constriction, these inhibitors were without effect on values of SNGFR and APR. In group 1 rats, reduction in mean renal arterial perfusion pressure (RAP) to approximately 65 mm Hg resulted in marked and proportional declines in SNGFR and APR. With equivalent reduction in RAP in group 2 rats, however, SNGFR fell to a lesser extent and APR tended to increase slightly above preconstriction values. Indomethacin administration was therefore associated with disruption of glomerulotubular balance. In view of the roughly equivalent declines in afferent arteriolar resistance measured in groups 1 and 2, the magnitude of increase in efferent arteriolar resistance (R(E)) appeared to be of major importance in determining the observed presence or absence of glomerulotubular balance. Thus, the lesser fall in SNGFR in group 2 than in group 1 was a result of the higher value for glomerular capillary hydraulic pressure in group 2, a consequence of the higher value of R(E). The higher average value for APR during reduced RAP in group 2 than in group 1 is also attributable to this pronounced rise in R(E), the effect of which was to augment the net reabsorptive pressure both by favoring higher postglomerular oncotic pressure and lower downstream (peritubular capillary) hydraulic pressure. Since intrarenal release of AII is enhanced when RAP declines, and because AII is known to raise R(E) selectively, it is likely that endogenous AII brought about the marked increase in R(E) in group 2, which was readily demonstrable only in indomethacin-treated rats, presumably because endogenous PG synthesis was suppressed. In keeping with this conclusion, when the action of endogenous AII was inhibited by saralasin in group 3 rats, reduction in RAP failed to induce a rise in R(E), so that net filtration and reabsorption pressures again declined proportionally, as did SNGFR and APR. The present evidence therefore suggests that glomerulotubular balance is influenced to an important extent by the prevailing vasomotor tone of the efferent arteriole.

Tubular transport processes in proximal tubules of hypothyroid rats. Micropuncture studies on isotonic fluid, amino acid and buffer reabsorption.

In three groups of rats: control animals (n=18), hypothyroid (TX) rats (n=21) 8–10 weeks after i. p. injection of Na131I (0.4–1 mCi), and hypothyroid rats (n=16) substituted with thyroxine (TX+T3, 50 μg/kg B.W. for 7 days) proximal tubule fluid reabsorption, and transtubular concentration difference of3H-l-histidine and3H-glycodiazine at zero net flux were measured. The effectiveness of TX was confirmed by delayed growth (200±12 as compared to 400±42 g B. W.), diminished plasma concentration of thyroxine (8.0 as compared to 53 μg/l), and increased plasma concentration of TSH (0.75 as compared to 0.15 mg/l).

Mechanism of inhibition of proximal tubule fluid reabsorption after exposure of the rat kidney to the physical effects of expansion of extracellular fluid volume.

The natriuresis and concomitant decline in absolute proximal reabsorption (APR) that occur in rats in response to saline loading are blunted markedly when renal perfusion pressure is reduced immediately before, but not after, the volume load. To ascertain the mechanism responsible for these differences between early clamp (EC) vs. late clamp (LC), intracapillary and interstitial determinants of peritubular capillary uptake of APR were measured in seven LC and seven EC Munich-Wistar rats before and after isotonic saline loading (80% body wt). With volume expansion in LC animals, we observed a marked decline in APR (averaging 11+/-1 nl/min), associated with large increases in urinary sodium excretion rate, which averaged 8+/-2 mueq/min. In EC, the changes in urinary sodium excretion rate (+1+/-0 mueq/min) and APR (-3+/-1 nl/min) with volume expansion were smaller in magnitude. Since peritubular capillary reabsorption coefficient and mean peritubular transcapillary hydraulic pressure difference did not change with saline loading in LC, the marked fall in APR was attributed primarily to a measured large decline in mean peritubular transcapillary oncotic pressure difference (deltapi). Despite an equivalent mean fall in deltapi with volume expansion in EC, near-constancy of APR was found to be associated with a simultaneous and equivalent decline in mean peritubular transcapillary hydraulic pressure difference (a consequence of decreased mean peritubular capillary hydraulic pressure), which effectively offset the fall in deltapi. These results demonstrate the importance of hydraulic pressure patterns of the peritubular capillaries in modulating APR and are consistent with the view that Starling forces across the postglomerular microcirculation play a fundamental role in determining APR.

Effect of volume expansion with NaCl or NaHCO3 on nephron fluid and Cl transport.

To assess the influence of plasma anions on nephron fluid and chloride transport following volume expansion (VE), rats were studied by micropuncture technique during hydropenia and after VE with NaCl (CVE) or NaHCO3 (BVE). VE with either solution produced increments in plasma volume, SNGFR, and fractional sodium excretion (FENa), and decrements in proximal and distal TF/P inulin ratio which were not different. The proximal transepithelial chloride ratio decreased similarly in CVE (from 1.34 to 1.16) and BVE (from 1.32 to 1.17). Following VE, proximal fractional Cl reabsorption decreased similarly in both CVE (-5.9%) and BVE (-7.4%). Early distal fractional Cl reabsorption also was decreased in CVE (-12%) but not in BVE (-1%). Fractional chloride excretion increased in CVE but not in BVE. Therefore, following VE plasma anion composition did not significantly modify either fluid reabsorption in proximal tubule or loop of Henle or urinary Na excretion. The fraction of sodium reabsorbed with chloride in the proximal tubule increased, and Cl conservation, primarily within the loop of Henle, can be maintained despite marked natriuresis.

Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat.

In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate. The resulting large increases in the efferent arteriolar oncotic pressure, piE, were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, deltaP. Equality of piE and deltaP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone. Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole. Tespite the marked increases in piE, absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure.