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Biomedical subjects

F G Knox

Publications and source records attributed to F G Knox.

At least 19 recordsLinked to original sources
PubMed1992

Intrarenal pressures during direct inhibition of sodium transport.

Renal interstitial hydrostatic pressure (RIHP) has been implicated in the regulation of sodium excretion. Studies using vasodilators and other maneuvers to increase RIHP have found a significant correlation between RIHP and sodium excretion. Since correlative studies do not prove a cause-and-effect relationship, it is not known whether the rise in sodium excretion in these studies is the result of increases in RIHP or if RIHP is elevated as a result of decreases in sodium and water reabsorption and increases in intratubular pressure. Therefore, the purpose of the present study was to determine whether elevation of intratubular hydrostatic pressures in response to direct inhibition of tubule transport with loop diuretics results in increases in RIHP in dogs and rats. Intrarenal hydrostatic pressures, renal hemodynamics, and sodium and water excretion were examined in dogs during intravenous administration of furosemide (3 mg/kg bolus followed by 0.03 mg.kg-1 x min-1) or bumetanide (60 micrograms/kg bolus followed by 1 microgram.kg-1 x min-1). Furosemide administration increased urinary flow rate (V; 0.10 +/- 0.02 to 4.6 +/- 0.97 ml/min), urinary sodium excretion (UNaV; 16 +/- 5 to 549 +/- 123 mu eq/min), and proximal tubule hydrostatic pressure (PT; 21 +/- 1 to 28 +/- 1 mmHg) but had no effect on RIHP (7.2 +/- 0.6 to 7.4 +/- 0.7 mmHg) or peritubular capillary hydrostatic pressure (14 +/- 1 to 14 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Mechanism of dopamine inhibition of renal phosphate transport.

Dopamine (DA) is natriuretic and phosphaturic. However, whether the effect of DA on Pi reabsorption is a consequence of its effect on sodium transport is not known. Therefore, this study was performed to determine the effect of DA on the maximal transport of phosphate (TmPi), and upon the capacity of renal proximal brush border membrane (BBM) for (Naextra-vesicular greater than Naintravesicular)-gradient-dependent transport of Pi, as compared with the transport of other solutes. Graded infusions of Pi (0, 1, 2, and 3 mumols/min) were given to thyroparathyroidectomized male Sprague-Dawley rats in the presence of vehicle (0.9% NaCl; N = 5), DA 15 micrograms/kg/min; N = 6), or parathyroid hormone ((PTH); 1 U/kg/min; N = 5). The TmPi for rats infused with DA (3.3 +/- 0.3 mumol/mL) was significantly less than the TmPi for saline control rats (4.4 +/- 0.2 mumol/mL). Rats infused with PTH exhibited the lowest TmPi (1.8 +/- 0.3 mumol/mL). No differences in sodium excretion were observed among any of the groups. Na-dependent Pi transport was studied in BBM vesicles (BBMV) prepared from rats fed a low-phosphate diet for 2 days that were anesthetized, acutely thyroparathyroidectomized, and systemically infused with DA (350 micrograms bolus, plus 35 micrograms/kg/min; N = 8), PTH (33 U/kg bolus, followed by a continuous infusion of 1 U/kg/min; N = 6), or vehicle (1 mL/kg bolus, plus 2 mL/h constant infusion of 0.9% NaCl; N = 8) for 90 min. DA significantly inhibited the Na cotransport of Pi by 22.4 +/- 4.1% (P less than 0.01) as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Dopamine enhances the phosphaturic response to parathyroid hormone in phosphate-deprived rats.

Phosphate deprivation results in a resistance to the phosphaturic effect of parathyroid hormone. Dopamine is phosphaturic and is synthesized by kidney proximal tubule, the nephron subsegment where parathyroid hormone inhibits phosphate transport. Thus, to test the hypothesis that phosphate deprivation is associated with low intrarenal dopamine synthesis and that dopamine infusion will overcome the resistance to the phosphaturic response to parathyroid hormone, the following study was performed. The effect of dietary phosphate intake on intrarenal dopamine synthesis, as reflected by urinary dopamine excretion, was determined. Rats were placed in metabolic cages (N = 5) and were fed a low-phosphate diet (0.07% Pi) for 4 days and then a high-phosphate diet (1.8% Pi) for 4 days. Twenty-four-hour urinary dopamine excretion was significantly lower in rats fed a low-phosphate diet (2.53 +/- 0.06 versus 4.10 +/- 0.30 micrograms/day). Further, the effect of dopamine infusion on the blunted phosphaturic response to parathyroid hormone was studied in rats fed a low-phosphate diet for 1, 2, and 3 days. Control clearances were taken 2 h after thyroparathyroidectomy; then, parathyroid hormone (33 U/kg plus 1 U/kg/min), dopamine (25 micrograms/kg/min), or parathyroid hormone plus dopamine were infused for 60 min. Changes in the fractional excretion of phosphate were significantly greater in rats fed a low-phosphate diet infused with parathyroid hormone plus dopamine than in rats fed a low-phosphate diet infused with parathyroid hormone alone (delta 27.9 +/- 5.8 versus 11.2 +/- 2.6% for day 1; 28.4 +/- 1.4 versus 7.1 +/- 3.6% for day 2; and 10.7 +/- 2.8 versus -0.2 +/- 0.2% for day 3; N = 5 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Acute renal denervation decreases tubular phosphate reabsorption.

Acute renal denervation (DNX) has been reported to increase urinary phosphate (Pi) excretion in rats with intact parathyroid glands and also in rats which were thyroparathyroidectomized (TPTX). The present study was performed to determine the effects of acute renal denervation on the tubular transport of Pi in rats in the absence of parathyroid hormone (PTH) and in rats with constant PTH levels. In TPTX rats, the reabsorbed Pi normalized for the glomerular filtration rate (Reab Pi/GFR) was 2.38 +/- 0.16 mumol/ml in the DNX kidney compared to 2.56 +/- 0.16 mumol/ml (p < 0.05) in the contralateral innervated (INN) kidney at endogenous plasma phosphate levels (n = 6). The lower values for the Reab Pi/GFR in the DNX kidney persisted at elevated plasma phosphate concentrations during phosphate infusions. Infusion of PTH resulted in markedly lower Reab Pi/GFR values in the innervated kidney (1.47 +/- 0.21 mumol/ml) at endogenous plasma phosphate levels than in the vehicle-infused group. Furthermore, the Reab Pi/GFR in the DNX kidney was decreased (1.21 +/- 0.14 mumol/ml, n = 6) compared to the contralateral INN kidney. These studies demonstrate that acute renal DNX decreases the tubular transport of Pi both in the absence and in the presence of constant PTH levels.

Absorption↗
PubMed1992

Stimulation of alpha 2-adrenoreceptors blunts the phosphaturic response to parathyroid hormone.

Acute renal denervation is phosphaturic and enhances the phosphaturic response to parathyroid hormone (PTH). Stimulation of alpha-adrenoreceptors inhibits the renal accumulation of 3,5-cyclic adenosine monophosphate (cAMP) in response to PTH. However, the effect of this blunted cAMP response by stimulation of alpha-adrenoreceptors on the phosphaturic response to PTH is not well understood. Therefore, the effect of alpha-adrenergic stimulation on the phosphaturic response to PTH was studied by infusion of PTH in the presence and absence of epinephrine plus propranolol. Sprague-Dawley rats were acutely thyroparathyroidectomized, and the left kidney was denervated. Stimulation of alpha-adrenoreceptors significantly blunted the phosphaturic response to PTH, decreasing the change in fractional excretion of phosphate (delta FEp) (21.2% +/- 1.3%, n = 8), as compared with the response to PTH alone (FEp, 30.0% +/- 2.4%, n = 7). In subsequent studies, yohimbine (an alpha 2-adrenoreceptor antagonist) or prazosin (an alpha 1-antagonist) were infused to dissociate alpha 1 from alpha 2-adrenoreceptor activity. Coadministration of yohimbine tended to restore the blunted phosphaturic response to PTH induced by alpha-adrenergic stimulation (delta FEp, 25.8% +/- 2.4%, n = 9), whereas addition of prazosin did not affect the blunted response (delta FEp, 16.1% +/- 4.5%, n = 7). We conclude that stimulation of alpha-adrenoreceptors blunts the phosphaturic response to PTH, most likely due to enhanced alpha 2-adrenoreceptor activity.

Animals↗
PubMed1991

Quantitation of the Na(+)-Pi cotransporter in renal cortical brush border membranes. [14C]phosphonoformic acid as a useful probe to determine the density and its change in response to parathyroid hormone.

To determine the density of Na(+)-Pi symporters in brush border membranes (BBM) from rat renal cortex, [14C] phosphonoformic acid [( 14C] PFA), a competitive inhibitor of Na(+)-Pi cotransport, was employed as a probe. The [14C]PFA binding was measured in BBM vesicles (BBMV) under equilibrated conditions (extra-vesicular Na+, K+, and H+ = intravesicular Na+, K+, and H+) to avoid modulatory effects of these solutes. BBMV were preincubated in media without or with addition of molar excess of Pi (greater than 20 times) to determine the Pi-protectable PFA-binding sites, and then [14C] PFA binding was determined. Only the [14C]PFA binding in the presence of Na+ displaceable by an excess of Pi was saturated and was independent of intravesicular volume of BBMV. This value denoted as "Pi-protectable Na(+)-[14C]PFA binding," was analyzed by Scatchard plot showing BmaxPFA = 375 +/- 129 pmol of PFA/mg protein, KDPFA = 158 +/- 18 microM; the Hill coefficient was congruent to 1. For Na(+)-dependent binding of [3H]phlorizin, in the same BBMV, Bmax = 310 +/- 37 pmol/mg protein and KD V 2.2 +/- 0.5 microM. BBMV prepared from cortex of thyroparathyroidectomized rats infused with phosphaturic doses of parathyroid hormone (PTH) were compared with vehicle-infused controls. Administration of PTH resulted in decrease of BmaxPFA (-38%) and of Na(+)-gradient-dependent uptake of 32Pi (-35%), but KDPFA was not changed. Neither BmaxPhl and KDPhl for Na(+)-phlorizin binding, nor the Na(+)-gradient-dependent uptake of [3H]D-glucose differed between PTH-treated and control rats. We conclude: (a) measurement of Pi-protectable Na(+)-[14C]PFA binding determines numbers and affinity of Na(+)-Pi symporters in renal BBMV; (b) the affinity of PFA for Na(+)-Pi symporter is similar to apparent affinity for Pi (KmPi), as determined from measurements of Na(+)-gradient-dependent 32Pi uptake by BBMV; (c) both Na(+)-Pi symporter and [Na+]D-glucose symporters are present within renal BBM in a similar range of density; (d) PTH decreases the number of Na(+)-Pi cotransporters in BBMV commensurate with the parallel decrease of Na(+)-gradient-dependent Pi transport, whereas the affinity of Na(+)-Pi symporters for Pi is not changed. These observations support the hypothesis that PTH decreases capacity for Na(+)-dependent Pi reabsorption by internalization of Na(+)-Pi symporters in BBM of renal proximal tubules.

Animals↗
PubMed1991

Laboratory experience for understanding the physiological basis of diuretic therapy.

A combined lecture and laboratory experience was designed to enhance medical school students' understanding of the physiological basis of diuretic therapy. Studies are performed by students in anesthetized dogs to determine the effects of four clinically useful diuretics on renal function. The objective of the experience is to 1) learn the mechanisms of action, clinical indications, and adverse effects of diuretics; 2) review the renal physiology of glomerular filtration and sodium metabolism; and 3) complete analysis and interpretation of experimental data. These sessions provide an effective practical educational experience in applying the scientific method to begin to understand the physiology and pharmacology of diuretics.

Animals↗
PubMed1991

Renal interstitial hydrostatic pressure and PGE2 in pressure natriuresis.

The present study tested the hypothesis that the presence of renal prostaglandin E2 (PGE2) is necessary for full natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during increased renal perfusion pressure (RPP). In control untreated pentobarbital-anesthetized dogs (n = 7), fractional excretion of sodium (FENa) was 1.17 +/- 0.48, 1.07 +/- 0.24, and 2.69 +/- 0.57% at RPP of 90, 122, and 148 mmHg, respectively. These changes in FENa were associated with effective renal blood flows (ERBF) of 1.43 +/- 0.20, 1.49 +/- 0.23, and 1.99 +/- 0.40 ml.min-1.g kidney wt-1, respectively. Similarly, glomerular filtration rate (GFR) was 0.53 +/- 0.10, 0.71 +/- 0.10, and 0.72 +/- 0.14 ml.min-1.g kidney wt-1, respectively. Treatment with indomethacin, a cyclooxygenase inhibitor, significantly lowered FENa to 0.45 +/- 0.13, 0.77 +/- 0.21, and 1.19 +/- 0.59% at RPP of 91, 121, and 146 mmHg, respectively. Additionally, indomethacin treatment lowered ERBF (0.51 +/- 0.15, 0.52 +/- 0.10, and 0.85 +/- 0.21 ml.min-1.g kidney wt-1) and GFR (0.28 +/- 0.09, 0.34 +/- 0.09, and 0.47 +/- 0.09 ml.min-1.g kidney wt-1) at low, middle, and high RPP, respectively. PGE2 replacement (n = 6) into renal artery at 0.01 microgram.min-1.kg body wt-1 returned FENa, ERBF, and GFR to control levels over the same range of RPP, whereas prostacyclin (PGI2) infusion (n = 7) at the same dose did not. RIHP was 4.2 +/- 1.2, 4.2 + 0.5, and 7.5 +/- 1.7 mmHg with increasing RPP in control untreated group and increased to similar levels with indomethacin treatment and during PGE2 or PGI2 replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Renal denervation enhances the phosphaturic effect of parathyroid hormone.

Hyperventilation/hypocapnia increases renal phosphate reabsorption and decreases the phosphaturic effect of parathyroid hormone (PTH). Recent studies suggest that the blunted phosphaturic effect of PTH in hyperventilated/hypocapnic rats may be mediated by the stimulation of renal beta-adrenoreceptors. In the present study, no differences in plasma catecholamine levels were detected in hyperventilated/hypocapnic rats as compared to hyperventilated/normocapnic rats. Therefore, studies were performed to determine the role of the renal nerves in the blunted phosphaturic effect of PTH in hyperventilated/hypocapnic rats. In clearance experiments in acutely thyroparathyroidectomized male Sprague-Dawley rats, PTH infusion increased the fractional excretion of phosphate (FEPi) in the denervated left kidney of hyperventilated/hypocapnic rats (n = 8), from 2.4 +/- 1.1 to 18.6 +/- 2.7%, as compared to 1.0 +/- 0.3 to 9.1 +/- 2.1% in the contralateral innervated kidney. Denervation of the left kidney in hyperventilated/normocapnic rats (n = 8) also significantly increased the phosphaturic response to PTH by 2.5 +/- 1.5 to 26.9 +/- 3.0% as compared to 0.9 +/- 0.5 to 18.6 +/- 2.6% in the contralateral innervated kidney. The phosphaturic responses to PTH were similar when comparing the denervated kidney in hyperventilated/hypocapnic rats with the innervated kidney of hyperventilated/normocapnic rats. Thus, renal denervation enhanced the phosphaturic effect of PTH in both hyperventilated/hypocapnic and hyperventilated/normocapnic rats. These results suggest that renal nerves play a role in the modulation of the phosphaturic effect of PTH.

Animals↗
PubMed1990

Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat.

Prostaglandin E2, when infused into the renal artery of the dog, is a vasodilator and increases both renal interstitial hydrostatic pressure and sodium excretion. Similar studies in the rat, however, have been inconclusive. The present study examined the effect of prostaglandin E2 infusion into the renal interstitium, by means of a chronically implanted matrix, on renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. Prostaglandin E2 was continuously infused directly into the kidney interstitium to mimic endogenous prostaglandin E2 production by renal cells. The maximum change in each of these parameters occurred when 10(-5) M PGE2 was infused. Renal blood flow increased from 4.70 +/- 0.91 to 5.45 +/- 0.35 ml/min (p less than 0.05) while renal interstitial hydrostatic pressure decreased from 3.9 +/- 0.4 to 2.6 +/- 0.5 mmHg (p less than 0.05) and fractional excretion of sodium decreased from 1.02 +/- 0.20 to 0.61 +/- 0.12% (p less than 0.05). Thus, the present study demonstrates that renal interstitial infusion of prostaglandin E2 increases total renal blood flow but decreases both renal interstitial hydrostatic pressure and urinary sodium excretion in the rat.

Animals↗
PubMed1990

Dissociation of renal interstitial hydrostatic pressure and natriuresis of atrial natriuretic factor.

The objective of these experiments was to test the hypothesis that renal interstitial hydrostatic pressure (RIHP) plays an important role in the natriuretic effect of atrial natriuretic factor (ANF) in anesthetized Wistar rats. Three groups of male Wistar rats were used in this study. Two groups were infused with different doses of ANF, and the third group was a time control. In all groups, one kidney was acutely decapsulated, and the contralateral kidney was used as control. Renal decapsulation was used to control RIHP. In one group, 3 micrograms.kg-1.h-1 of synthetic ANF were infused intravenously (iv) and produced a plasma level of ANF (PANF) of 810 +/- 186.5 pg/ml. This pharmacological dose of ANF produced a significant increase in RIHP of the control kidney from 9.5 +/- 0.8 to 11.1 +/- 1.3 mmHg (P less than 0.05) but not in the decapsulated kidney [from 7.1 +/- 0.6 to 8.1 +/- 0.9 mmHg, not significant (NS)]. However, the changes in fractional excretion of sodium (FENa) and urine flow rate (V) as a result of ANF infusion were similar in both kidneys. In the decapsulated kidney, FENa and V increased by 1.53 +/- 0.41% and 26.21 +/- 5.98 microliters/min, respectively, from control to ANF infusion periods. In the control kidney, FENa and V increased by 1.60 +/- 0.28% and 31.61 +/- 5.87 microliters/min, respectively, from control to ANF infusion periods. In the second group, 1 microgram.kg-1.h-1 iv of synthetic ANF was infused and produced 165.2 +/- 29.3 pg/ml of PANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Renal interstitial hydrostatic pressure and ANF in exaggerated natriuresis of the SHR.

The Okamoto spontaneously hypertensive rat (SHR) has exaggerated natriuretic and diuretic responses to acute volume expansion in comparison with the Wistar-Kyoto (WKY) rat. The objective of these experiments was to determine the role of renal interstitial hydrostatic pressure (RIHP) and atrial natriuretic factor (ANF) in these natriuretic and diuretic responses of the SHR and the WKY rat. Two groups each of SHRs and WKY rats were used in this study. In one group of each, both kidneys were acutely decapsulated, and in the remaining two groups the renal capsules were left intact (control). In both control SHR (n = 6) and WKY (n = 7) groups, volume expansion was associated with a significant increase in RIHP (from 5.0 +/- 0.5 to 7.1 +/- 0.6 mmHg in SHR group and from 6.0 +/- 0.5 to 9.4 +/- 0.3 mmHg in WKY rat group) and a high level of plasma ANF (PANF). The increase in RIHP was significantly lower in the control SHR group compared with that of control WKY rat group (2.1 +/- 0.4 vs. 3.5 +/- 0.3 mmHg; P less than 0.05), whereas PANF was significantly higher in the SHR group (848 +/- 151 pg/ml) compared with that of the WKY group (503 +/- 37 pg/ml) at the end of the volume-expansion period. When the increase in RIHP that occurs during volume expansion in the SHR is blunted by acute bilateral renal decapsulation, the natriuretic and diuretic responses are significantly attenuated despite levels of PANF that are similar to those measured in the control SHR group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of propranolol on phosphate reabsorption by superficial nephron segments in response to parathyroid hormone in phosphate-deprived rats.

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone. The decreased phosphaturic response to parathyroid hormone in rats fed a low phosphate diet for 1 day can be restored by propranolol infusion. Free-flow micropuncture studies were performed to localize the nephron site of restoration of the phosphaturic effect of parathyroid hormone by propranolol in rats deprived of phosphate for one day. In animals fed low phosphate diet and in the presence of parathyroid hormone, propranolol infusion did not change phosphate delivery to the late proximal tubule; however, fractional delivery of phosphate to the early distal tubule was significantly increased from 18.3 +/- 2.9 to 32.2 +/- 4.1%. In rats fed a normal phosphate diet, propranolol infusion did not change phosphate delivery along the nephron. We conclude that the restoration of the phosphaturic effect of parathyroid hormone by propranolol infusion in rats deprived of phosphate for 1 day is primarily due to decreased reabsorption of phosphate by superficial loop segments, most likely the pars recta segment of the proximal tubule.

Absorption↗
PubMed1979

Alkaline phosphatase in adaptation to low dietary phosphate intake.

Previous findings suggest that alkaline phosphatase (Alk Pase) may be involved in phosphate transport. Since phosphate reabsorption is enhanced in the kidney and duodenum of animals stabilized on a low-phosphorus diet (LPD), Alk Pase was measured in the kidney, small intestine, and other tissues in LPD rats. In particulate fractions from the renal cortex, intestine, renal medulla, liver, and heart ventricle from LPD rats the activity of Alk Pase was significantly increased but the activities of other plasma membrane enzymes were not different between control and LPD groups. The increased Alk Pase in the renal cortex was localized to the brush border of the proximal tubule histochemically and by measurement of Alk Pase in brush-border preparations. Also in the renal cortex, typical enzymes associated with mitochondria, lysosomes, and cytosol were unchanged with the exception of cytosolic adenosine 3',5' cyclic-monophosphate phosphodiesterase, which was increased in LPD rats. Alk Pase in the renal cortex and intestine may play a role in the enhanced phosphate reabsorption in LPD animals.

Alkaline Phosphatase↗
PubMed1979

Collecting duct sodium reabsorption in deoxycorticosterone-treated rats.

In vitro studies of isolated, perfused, cortical collecting tubules have demonstrated that prior chronic deoxycorticosterone acetate (DOCA) treatment increases sodium reabsorption in this nephron segment, yet sodium balance in vivo is maintained. To evaluate the effect of chronic DOCA treatment on collecting duct sodium reabsorption in vivo, we compared fractional sodium delivery (FD(Na)%) out of the superficial late distal tubule with the fraction of sodium remaining at the base and the tip of the papillary collecting duct during extracellular fluid volume expansion in untreated, salt-treated, and DOCA-salt-treated rats. In untreated rats, FD(Na)% to the distal tubule was 6.5+/-1.0%, and to the base was 8.7+/-1.6% (Delta2.2+/-0.9%, P < 0.05). FD(Na)% to the tip was 4.9+/-1.1%, significantly less than FD(Na)% to the base (Delta3.7+/-1.1%, P < 0.01). In salt-treated rats, FD(Na)% to the distal tubule was 8.3+/-0.8%, and to the base was 10.4+/-1.1%. FD(Na)% to the tip was 5.9+/-0.6%, significantly less than FD(Na)% to the base (Delta 4.6+/-1.0%, P < 0.005). In DOCA-salt-treated rats, FD(Na)% to the distal tubule was 16.1+/-2.6% and to the base was 9.5+/-1.9% (Delta 6.6+/-1.7%, P < 0.005). FD(Na)% to the tip was 5.9+/-1.2%, also significantly less than FD(Na)% to the base (Delta 3.6+/-1.1%, P < 0.01). We conclude that (a) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than in untreated or salt-treated rats; (b) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than to the base of the papillary collecting duct, suggesting stimulation of sodium reabsorption in the cortical and(or) outer medullary collecting duct; and (c) sodium reabsorption by the papillary collecting duct is unaffected by chronic DOCA-salt treatment in the volume-expanded rat.

Absorption↗