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Sodium balance may affect the response of single-nephron filtration rate (SNFR) to changes in renal arterial pressure (deltaRAP) when the SNFR is measured in the absence of orthograde fluid delivery from the proximal tubule. This thesis was tested in sodium-depleted and -expanded dogs given furosemide, Doca, and low- or high-salt diets, respectively. After 7 days of treatment, renal renin content was significantly greater in the sodium-depleted group (delta = 23.5 +/- 7.4 DU [dog units]/g kidney). Glomerular filtration rate and renal plasma flow were similar in both groups following changes in RAP of 29 +/- 4 and 29 +/- 3 mmHg in the sodium-depleted and -expanded groups, respectively. SNFR at high RAP was not different from SNFR at low RAP in the sodium-depleted group (delta = -0.2 +/- 4.9 nl/min) and slightly, but significantly, greater in the sodium-expanded group (delta = 7.6 +/- 2;1 nl/min). However, the response of SNFR was similar to that of whole-kidney filtration rate. Furthermore, the autoregulatory response (deltaSNFR/deltaRAP) was not significantly different between the groups but was significantly greater than the response calculated for RAP below the range studied. It is concluded that an autoregulatory response of SNFR, in the absence of orthograde fluid delivery from the proximal tubule, is observed in both sodium-depleted and -expanded dogs.

We tested the hypothesis that greater phosphate delivery from deep nephrons than from superficial nephrons contributes to the addition of phosphate to the collecting system during phosphate loading. In the first group of eight anesthetized Munich-Wistar rats infused with phosphate and parathyroid hormone (PTH), fractional delivery of phosphate (FDP%) from superficial distal tubules was 56 +/- 6%, significantly less than the amount appearing in the urine, 67 +/- 6% (P less than 0.01). In the second group of six rats, we determined whether this addition of phosphate could be accounted for by a higher FDP% from the deep nephrons. Free-flow micropuncture collections were taken from deep nephrons (ascending limb of the loop of Henle in the papilla), superficial nephrons (distal tubules in the cortex), and urine (duct of Bellini). The FDP% to the ascending limb of the loop of Henle in deep nephrons was 78 +/- 10%, significantly greater than to the distal convoluted tubules in superficial nephrons, 51 +/- 6% (P less than 0.005), and the fractional excretion of phosphate in urine, 72 +/- 10% (P less than 0.05). Although a difference between FDP% in superficial and deep nephrons due to reabsorption in the ascending limb of the loop of Henle cannot be ruled out from the present data, other studies indicate that this interpretation is unlikely. We conclude that greater phosphate delivery by deep nephrons contributes to the addition of phosphate to the collecting system of phosphate-loaded rats.

The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes.

These studies were performed to determine whether a role for increased renal plasma flow (RPF) in the regulation of glomerular filtration rate (GFR) could be demonstrated in dogs by infusing the polypeptide hormone secretin, a vasodilator that has been reported to increase GFR. Differences between control and recollection periods were compared by paired t test in five time-control dogs (group 1) and 10 secretin dogs (group 2). In group 2, secretin (100 mU . kg-1 . min-1, ia) significantly increased single-nephron glomerular filtration rate (SNGFR) 11.1 +/- 3.1 nl/min (20%) and glomerular plasma flow 59 +/- 11 nl/min (26%). Similar increases in GFR (26%) and RPF (29%) were observed. Secretin also increased glomerular capillary pressure 5.2 +/- 0.8 mmHg and free-flow proximal tubule pressure 5.5 +/- 1.0 mmHg. Secretin did not significantly affect average effective filtration pressure (EFP) but significantly increased the ultrafiltration coefficient (Kf) 0.74 +/- 0.14 nl . min-1 . mmHg-1. These differences were significantly greater than those observed in group 2. It is concluded that secretin increased SNGFR primarily by an effect on Kf. This is consistent with the marked effect that Kf is predicted to have on glomerular filtration in dogs. The maintenance of EFP agrees with other vasodilator studies and indicates that GFR is only moderately dependent on plasma flow in dogs.

Elevated levels of parathyroid hormone (PTH) often are associated with reduced glomerular filtration rate (GFR) in humans. Although PTH has been reported to reduce the ultrafiltration coefficient (Kf) in rats, GFR declined only if they were plasma expanded. In contrast, PTH does not reduce GFR in dogs, despite filtration pressure disequilibrium. To evaluate this apparent discrepancy, the determinants of GFR were measured in acutely thyroparathyroidectomized dogs. In the absence (n = 8) and presence (n = 10) of synthetic bovine PTH, GFR was 29 +/- 3 and 26 +/- 2 ml/min; Single nephron glomerular filtration rate was 58 +/- 4 and 51 +/- 3 nl/min; glomerular plasma flow was 248 +/- 22 and 250 +/- 24 nl/min; glomerular capillary pressure was 58 +/- 2 and 61 +/- 3 mmHg; Bowman's space pressure was 19 +/- 2 and 19 +/- 1 mmHg; and systemic oncotic pressure was 19 +/- 0.8 and 18 +/- 0.5 mmHg. Average effective filtration pressure (EFP) was significantly greater in the presence (18.6 +/- 1.3 mmHg) than in the absence (14.6 +/- 0.9 mmHg) of PTH. Therefore, Kf per glomerulus calculated from these data was significantly (P less than 0.01) less in the presence than in the absence of PTH (2.91 +/- 0.29 and 3.98 +/- 0.16 nl X min-1 X mmHg-1, respectively). It is concluded that PTH reduced Kf. Whereas this effect predicts reduced GFR in dogs, given filtration pressure disequilibrium, a concomitant increase in EFP maintained GFR in the present study.

Micropuncture techniques were used to evaluate the determinants of glomerular filtration in hydropenic dogs. Stop-flow and servo-null techniques were used to estimate the glomerular capillary and proximal tubule hydrostatic pressures. The validity of stop-flow estimates was verified by comparisons with direct puncture of glomerular capillaries in Munich-Wistar rats. Efferent arteriolar oncotic pressure was calculated from the filtration fraction and systemic protein concentrations. This calculation was verified in separate experiments by measurement of the protein concentration in blood collected directly from efferent arterioles. In 14 dogs, estimated glomerular capillary pressure (GCP) averaged 65.8 +/- 2.9 mmHg and proximal tubule pressure (PT) averaged 20.5 +/- 1.3 mmHg. The net hydrostatic filtration pressure (GCP - PT) of 45.3 +/- 2.7 mmHg was significantly higher than the efferent arteriolar oncotic pressure (piEA) of 33.2 +/- 2.8 mmHg (P less than .001). These findings indicate that filtration dynamics in the dog are characterized by filtration pressure disequilibrium.

Most renal vasodilators are natriuretic. However, secretin increases renal blood flow (RBF) markedly but produces only a very slight increase in sodium excretion (UNaV). To investigate this observation further, the relationship between vasodilatation, interstitial pressure (IP), and UNaV was studied in dogs. Intrarenal infusion of secretin increased RBF (delta=107+/-19 ml/min). The IP, as measured from chronically implanted polyethylene matrix capsules, was not significantly changed (delta=-0.3+/-0.5 mmHg). UNaV was slightly, although significantly, increased (delta=19+/-4 mueq/min). Following a similar increase in RBF with an intrarenal infusion of acetylcholine (ACh), IP and UNaV increased markedly (delta=8.2+/-0.8 mmHg and 174+/-23 mueq/min, respectively). Neither secretin nor ACh) altered glomerular filtration rate or blood pressure. Both secretin and ACh produced comparable increases in peritubule capillary(delta=5+/-1 and 7.5+/-1.4 mmHg, respectively) and free-flow tubule pressure (delta=7+/-2 and 9.5+/-1.4 mmHg, respectively). In summary, the usual relationship between vasodilatation and IP was dissociated during secretin infusion, whereas the relationship between IP and natriuresis was not dissociated.

Recently, a paradoxical effect of dietary salt intake on the natriuresis following hypertonic saline infusion was observed in rats. In these experiments the effects of alterations in dietary sodium on the natriuretic response to a hypertonic saline load was studied in dogs. Dogs maintained on a high-sodium diet did not have a significantly different natriuresis than those on a low-sodium diet. When differences in sodium balance were amplified by the use of deoxycorticosterone, furosemide, and manipulation of dietary sodium, dogs in positive sodium balance showed a significantly enhanced initial excretion of sodium followed by a reversal of the pattern. Consequently, the cumulative sodium excretion was not different between low- and high-sodium groups. Since the cumulative natriuretic response to isotonic saline infusion was larger in dogs in positive sodium balance compared to those in negative sodium balance, the failure to detect a difference following hypertonic saline infusion was probably because of the increased plasma sodium concentration.

The first objective of this study was to examine the effects of furosemide on renal phosphate excretion in the presence and absence of a constant level of parathyroid hormone (PTH) while extracellular fluid volume was held constant. In the absence of PTH, furosemide did not significantly increase fractional phosphate excretion (FEP%, 4.2 +/- 2.7 to 6.2 +/- 1.9%; five dogs). In the presence of PTH, furosemide increased FEP% from 23.4 +/- 3.7 to 33.8 +/- 6.0% (P less .025; five dogs). Thus, the phosphaturia induced by furosemide was dependent on the presence of PTH. The second objective was to evaluate the hypothesis that furosemide exerts its phosphaturic effect through carbonic anhydrase inhibition, and therefore we tested for additivity of the phosphaturic effect of furosemide, and acetazolamide. In the presence of a constant level of PTH, acetazolamide increased FEP % from 24.5 +/- 1.8% to 40.7 +/- 5.1% P less than .025, five dogs. The subsequent administration of furosemide did not further increase FEP%, delta 3.3 +/- 8.9%; NS. Thus, the phosphaturic effect of furosemide was not additive to that of acetazolamide, indicating that acetazolamide and furosemide may share similar mechanisms for inhibiting phosphate reabsorption.