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Biomedical subjects

F G Knox

Publications and source records attributed to F G Knox.

At least 91 records · Page 5Linked to original sources
PubMed1989

Rat atrial natriuretic factor (ANP-III) inhibits phosphate transport in brush border membrane from superficial and juxtamedullary cortex.

Previous studies have shown that administration of synthetic atrial natriuretic factor (ANF, 101-126) decreases sodium-dependent phosphate transport across renal brush border membrane vesicles (BBMV) in rats fed a normal or low phosphate diet. In the present study, infusion of rat ANF (atriopeptin III (ANP-III), 103-126 rat ANF) to rats fed a normal phosphate diet caused natriuretic and phosphaturic effects similar to those of ANF (101-126), but unlike ANF (101-126) did not increase the glomerular filtration rate. The effect of ANP-III infusion on sodium-dependent transport of phosphate was also determined in BBM vesicles isolated from the superficial cortex (BBMV-SC) and juxtamedullary cortex (BBMV-JM). The results indicate that ANP-III decreases phosphate transport across BBMV-SC and BBMV-JM similarly (20-24%). However, it had no effect on sodium-dependent transport of proline in these vesicles. The infusion of ANP-III to rats fed a normal phosphate diet inhibits phosphate uptake both in BBMV-SC and BBMV-JM and causes phosphaturia without increments in glomerular filtration rate.

Animals↗
PubMed1989

Effect of synthetic atrial natriuretic factor on superficial and deep proximal tubule sodium reabsorption.

The effects of synthetic atrial natriuretic factor (ANF) on sodium reabsorption by deep and superficial proximal tubules were examined in the rat. In response to ANF infusion (4 micrograms/kg/hr), the urinary fractional excretion of sodium increased from 1.21% +/- 0.53% to 3.48% +/- 0.48%, p less than 0.05 (n = 12). Fractional delivery of sodium (FDNa) from the deep proximal tubule was 25.9% +/- 3.7% before and 33.7% +/- 3.4% after ANF infusion. In time control animals, FDNa from deep proximal tubules was 34.3% +/- 3.0% and 28.5% +/- 4.0% respectively (n = 12). The change in FDNa from deep proximal tubules during ANF infusion (increase of 7.8% +/- 3.9%) was significantly different from the change in control animals (decrease of 5.8% +/- 3.1%) (ANF infusion vs control, delta 13.7% +/- 4.9%, p less than 0.05). No significant change was observed in FDNa in the superficial proximal tubule either during ANF infusion or in control animals. In summary, ANF infusion increased urinary fractional sodium excretion; however, fractional sodium reabsorption by the proximal tubule of superficial nephrons was unchanged. In contrast, sodium delivery to the point of micropuncture in the descending limb of Henle's loop of deep nephrons was increased, as compared with controls, suggesting inhibition of sodium reabsorption by proximal tubules of deep nephrons.

Absorption↗
PubMed1988

Three-dimensional canine renovascular structure and circulation visualized in situ with the dynamic spatial reconstructor.

The dynamic spatial reconstructor--a unique, high speed, volume-scanning, X-ray computed tomographic imaging system--was utilized to examine canine renovascular anatomy and renal circulation in situ. In each of the four kidneys examined in this study initial scans were done during bolus injections of angiographic contrast material into the renal artery. A subsequent scan was then performed following an injection of methyl-methacrylate-based casting compound that had been contrast enhanced with ethiodol. After the scans, each kidney was removed, and its parenchyma was digested in potassium hydroxide to expose the vascular cast. Comparison of casts with their reconstructed images and with images obtained during injection of contrast material showed that interlobar arteries and occasionally arcuate arteries could be clearly detected. Although discrete vessels less than 1 mm in diameter could not be resolved, dynamic changes in parenchymal distribution of density during passage of contrast material allowed interpretation of flow through the multiple capillary beds of the kidney. Such analysis indicated that maximal density was in the outer-middle zone of the cortex throughout the duration of the scan. Analysis of artery-to-vein transit time showed arrival of contrast material in the renal vein as soon as 3 sec, and continuation for longer than 8 sec, after the renal artery bolus. In conclusion, renal circulation in the dog can be discretely visualized with the dynamic spatial reconstructor up to the level of the arcuate arteries; however, capillary flow as a whole can be followed through the cortex, and the results suggest the presence of both rapid and slow components of peritubular circulation.

Animals↗
PubMed1988

Mechanisms affecting the development of renal cystic disease induced by diphenylthiazole.

To provide information on the possible influence that hypertension or its treatment might have on the development of cysts in autosomal dominant polycystic kidney disease, we studied the effects of the sodium content of the diet, DOCA-salt hypertension, renovascular hypertension, and the administration of enalapril or furosemide on the development of 2-amino-4-5-diphenylthiazole (DPT)-induced renal cystic disease. DOCA-salt hypertension caused vascular and glomerular lesions and proteinuria, but it did not enhance the development of cysts. Cytogenesis was enhanced in experimental conditions where the renin-angiotensin system is known to be activated. On the other hand, interventions known to suppress the renin-angiotensin system lessened the development of cysts. We hypothesize that this effect might be mediated by intrarenal angiotensin II and its capacity to promote cell growth and to control the postglomerular vascular resistances and the compliance of the renal interstitium.

Animals↗
PubMed1988

Beta-receptors in resistance to phosphaturic effect of PTH in respiratory alkalosis.

Respiratory alkalosis results in a resistance to the phosphaturic effect of parathyroid hormone (PTH) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). The present studies evaluated the role of the beta-adrenergic system in that resistance phenomenon. In clearance experiments on acutely thyroparathyroidectomized male Wistar rats, respiratory alkalosis blunted the PTH-mediated increase in absolute and fractional excretion of phosphate (FEPi). Propranolol infusion restored the phosphaturic response to PTH:FEPi, 0.8 +/- 0.3 vs. 8.1 +/- 2.5% (P less than 0.005). Similarly, the increase of FEPi during cAMP infusion was also diminished by respiratory alkalosis: FEPi, 15.5 +/- 2.2 vs. 5.5 +/- 1.1% (P less than 0.005). This hypophosphaturic effect of respiratory alkalosis in the presence of cAMP was not observed in rats infused with propranolol compared with the period of normal ventilation: FEPi, 21.1 +/- 1.7 vs. 15.3 +/- 1.6 (P less than 0.02). Also, during the infusion of the highly selective beta 2-adrenoceptor antagonist, ICI 118,551, cAMP was phosphaturic in respiratory alkalosis compared with FEPi in the absence of the antagonist: FEPi, 13.0 +/- 2.5 vs. 5.5 +/- 1.1% (P less than 0.02). Finally, the infusion of the beta 2-agonist, fenoterol, to the normally ventilated rats significantly decreased FEPi in cAMP-infused rats in comparison to the absence of the agonist: FEPi, 4.0 +/- 0.7 vs. 22.1 +/- 2.6% (P less than 0.001). We conclude that the resistance to the phosphaturic effect of PTH and cAMP in respiratory alkalosis is mediated by beta-adrenoceptors.

Alkalosis↗
PubMed1988

Renal interstitial hydrostatic pressure during pressure natriuresis in hypertension.

The objective of this study was to test the hypothesis that changes in renal perfusion pressure (RPP) are not fully transmitted to the renal interstitium in spontaneous hypertension in comparison with normotensive states. Okamoto spontaneously hypertensive and normotensive Wistar-Kyoto rats were used in this study. Renal interstitial hydrostatic pressure (RIHP) was measured directly and continuously via a polyethylene matrix that was implanted chronically in the left kidney 3 wk before RIHP measurement. When RPP was allowed to increase from 136 +/- 0.5 to 162 +/- 1.3 mmHg in male spontaneously hypertensive rats, RIHP was not significantly changed from 3.7 +/- 0.9 to 4.6 +/- 1.1 mmHg, and fractional excretion of sodium (FENa) increased significantly from 0.26 +/- 0.12 to 0.65 +/- 0.15% (P less than 0.05). When RPP was allowed to change from 104 +/- 0.9 to 127 +/- 1.3 mmHg in male Wistar-Kyoto rats, RIHP increased markedly from 4.0 +/- 0.3 to 7.2 +/- 0.4 mmHg (P less than 0.05), and FENa was significantly elevated from 0.27 +/- 0.08 to 2.02 +/- 0.55% (P less than 0.05). In conclusion, spontaneously hypertensive rats have a blunted increase in RIHP and pressure natriuresis response in comparison with Wistar-Kyoto rats. Thus, in Okamoto spontaneously hypertensive rats, the effect of RPP on RIHP is attenuated, leading to a blunted pressure natriuresis response.

Animals↗
PubMed1988

Prostaglandin blockade blunts the natriuresis of elevated renal interstitial hydrostatic pressure.

Previous studies have shown that renal interstitial volume expansion (RIVE) increases renal interstitial hydrostatic pressure and urinary sodium excretion. In the present study we investigated whether blockade of prostaglandin synthesis inhibits the increase in fractional sodium excretion induced by RIVE. Expansion of the renal interstitial volume was achieved by injecting 50 microliters of 2.5% albumin solution into a polyethylene matrix chronically implanted in the left kidney. Fractional sodium excretion (FENa), renal interstitial hydrostatic pressure (PI), and urinary prostaglandin excretion (UPGE2) were measured before and after RIVE in eight control, seven meclofenamate-treated, and eight indomethacin-treated rats. RIVE in the control animals resulted in significant increases in PI (delta + 4.2 +/- 0.8 mmHg), in FENa (delta + 1.02 +/- 0.27%), and in UPGE2 (% delta + 150 +/- 38%) without significant changes in glomerular filtration rate. Inhibition of prostaglandin synthesis with meclofenamate or indomethacin attenuated the natriuretic response and blocked the increase in UPGE2 associated with RIVE. In summary, direct increases in renal interstitial hydrostatic pressure increase UPGE2 and urinary sodium excretion. This natriuretic response is markedly diminished by inhibition of prostaglandin synthesis. These studies suggest that prostaglandin synthesis may have an important role in mediating the natriuretic effect of increased renal interstitial hydrostatic pressure during renal interstitial volume expansion.

Animals↗
PubMed1988

Effect of direct increases in renal interstitial hydrostatic pressure on sodium excretion.

This study examined the effect of increases in renal interstitial hydrostatic pressure (PI) on sodium excretion (UNaV) utilizing a direct technique for increasing renal interstitial volume. PI was increased by renal interstitial volume expansion (RIVE) via injection of 50 microliters of a 2% albumin in saline solution into the renal interstitium through a chronically implanted interstitial catheter. RIVE resulted in a stable increase in PI (4.6 +/- 0.4 to 9.4 +/- 0.8 mmHg) that was sustained over a 30- to 40-min period without significant changes in renal blood flow or glomerular filtration rate. Increases in PI were associated with significant increases in urine flow (13.8 +/- 3.4 to 31.7 +/- 5.0 microliters/min) and UNaV (2.3 +/- 0.6 to 6.2 +/- 1.1 micro eq/min) and fractional excretion of Na (2.6 +/- 0.8 to 6.9 +/- 1.5%). To determine the importance of albumin in maintaining an elevated PI, the effects of renal interstitial injections of saline were compared with albumin in saline solution. Injection of 50 microliters of saline into the renal interstitium had no sustained effect on PI. Injection of 2% albumin in saline solution in the same group of rats resulted in significant elevations in PI and UNaV. These data indicate that direct increases in PI via renal interstitial volume expansion result in significant increases in UNaV, thus supporting a role for PI in controlling UNaV.

Animals↗
PubMed1988

Effect of cAMP analogue infusion on phosphate reabsorption in phosphate-deprived rats.

The present study was performed to compare the effects of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (cAMP analogue) and parathyroid hormone (PTH) infusion on segmental phosphate reabsorption in phosphate-deprived rats. Micropunctures of the late proximal and the early distal tubules were performed in acutely thyroparathyroidectomized (TPTX) rats fed either a normal (NPD) or low phosphate diet (LPD), and the phosphaturic response to infusion of PTH and cAMP analogue was evaluated. In NPD rats, PTH (n = 10) and the cAMP analogues (n = 11) markedly increased urinary phosphate excretion, due to inhibition of phosphate reabsorption along the proximal convoluted tubule and pars recta. In phosphate-deprived rats, PTH (n = 10) or the cAMP analogue (n = 11) did not increase urinary phosphate excretion. However, PTH and the cAMP analogue inhibited phosphate reabsorption along the proximal convoluted tubule but not in the pars recta in phosphate-deprived rats. We conclude that cAMP analogue infusion mimics the effect of PTH infusion on phosphate reabsorption along the proximal convoluted and proximal straight tubule in normal and phosphate-deprived rats. The resistance to the phosphaturic effect of PTH and cAMP infusions is a result of a blunted inhibition of phosphate reabsorption by the proximal convoluted tubule and also an increased phosphate reabsorption by the proximal straight tubule.

Animals↗
PubMed1988

Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo.

We examined whether phosphonoformate (PFA) can cause phosphaturia through its direct action on brush-border membrane (BBM) in vivo. Infusion of PFA or of parathyroid hormone (PTH) to thyroparathyroidectomized rats caused a marked increase in fractional excretion of phosphate without changes in excretion of Na+ or of GFR. The PFA-induced phosphaturia was not accompanied by an increase in urinary adenosine-3',5'-cyclic monophosphate (cAMP); moreover, PFA added in vitro did not influence the PTH-sensitive adenylate cyclase and cAMP-phosphodiesterase in proximal convoluted tubules. In BBM vesicles (BBMV) from rats with PFA-elicited phosphaturia, neither the rate of Na+-Pi symport nor Na+-dependent binding of [14C]PFA on BBMV was changed, whereas in BBMV from PTH-infused rats the Vmax of Na+-Pi symport decreased. PFA is almost completely ultrafiltrable; no metabolic transformation of PFA was detected after [14C]PFA exposure to rat renal cortical slices, homogenate, or to blood. We conclude that PFA causes phosphaturia by direct inhibition of Na+-Pi symport across BBM in proximal tubules, acting from the luminal side. Thus PFA (foscarnet) has a unique direct mechanism of phosphaturic effect, via its action on Pi reabsorption in proximal tubules in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Effect of intrarenal volume expansion on proximal sodium reabsorption.

The objective of the present study was to examine the effect of direct expansion of the renal interstitial volume on sodium reabsorption by proximal tubules of superficial and deep nephrons in the absence of systemic extracellular volume expansion. Renal interstitial volume expansion was achieved by injection of 50 microliter of 2.5% albumin in 0.9% saline into the renal interstitium via a polyethylene matrix that was chronically implanted in the interstitium of the rat kidney. Renal interstitial volume expansion increased renal interstitial hydrostatic pressure from 3.8 +/- 0.5 to 6.8 +/- 1.1 mmHg, P less than 0.05 (n = 5 rats). Fractional reabsorption of sodium by the superficial late proximal tubule decreased from 45.7 +/- 5.6 to 34.2 +/- 5.4%, P less than 0.05, and by the proximal tubule and descending limb of Henle's loop of deep nephrons it decreased from 73.9 +/- 2.9 to 57.2 +/- 6.3%, P less than 0.05 (n = 8 rats). Thus expansion of the renal interstitial volume increased renal interstitial hydrostatic pressure and decreased sodium reabsorption by the proximal tubules of superficial and deep nephrons.

Animals↗
PubMed1988

Mechanisms underlying pressure-related natriuresis: the role of the renin-angiotensin and prostaglandin systems. State of the art lecture.

It has long been known that increments in renal perfusion pressure can induce an elevation of urine sodium excretion without changing renal blood flow or glomerular filtration rate. The mechanism underlying this pressure-related natriuresis remains undefined, although the interest in its elucidation has been stimulated by the notion that it may constitute the central phenomenon through which the kidney regulates blood volume and, thereby, blood pressure. Recently, the use of novel experimental techniques has disclosed some important clues about changes in renal hemodynamics that, along with changes in renal humoral regulators, allow us to visualize a possible sequence of events responsible for pressure-related natriuresis. According to this hypothesis, the autoregulatory responses responsible for maintaining glomerular filtration rate are elicited in preglomerular vasculature by changes in renal perfusion pressure. These myogenic responses are coupled through Ca2+ entry in juxtaglomerular cells with inversely related changes in the release of renin and, consequently, with the amount of angiotensin II generated in renal interstitium. The release of renin from juxtaglomerular cells is modulated by the synthesis of prostaglandin I2 from the adjacent endothelial cells. Interstitial angiotensin II could influence sodium tubular reabsorption directly by stimulating sodium transport in proximal renal tubules and indirectly by altering medullary blood flow and, thereby, medullary interstitial pressure. In the renal medulla, the effects of interstitial pressure on sodium reabsorption can be amplified by the release of prostaglandin E2 from interstitial cells. A deficient regulation of this relationship could result in a shift of the pressure-natriuresis curve, leading to hypertension.

Angiotensin II↗
PubMed1988

Natriuretic effect of atrial natriuretic peptide in diabetes insipidus rats.

Washout of the solute concentration gradient in the renal medullary interstitium has been suggested to play a role in mediating the natriuretic response to atrial natriuretic peptide (ANP). The purpose of this study was to determine the effects of ANP 8-33 on sodium excretion in Brattleboro diabetes insipidus (DI) rats, in which medullary tonicity is known to be decreased as compared to Long-Evans (LE) control rats. Basal urine osmolality (Uosm) was significantly lower in DI rats as compared to LE rats (123 +/- 6 vs 673 +/- 38 mOsm/kg). Infusion of ANP 8-33 at a rate of 4 micrograms/kg/hr for 60 min resulted in a significantly greater increase in UnaV (delta 6.1 +/- 1.2 vs delta 2.9 +/- 0.7 microEq/min) and urine flow (delta 40 +/- 12 vs delta 8 +/- 7 microliter/min) in the LE rats than in the DI rats. The greater natriuresis occurred in the LE rats despite no significant change in Uosm. Fractional lithium reabsorption (an indicator of proximal sodium reabsorption) decreased similarly in both groups. Infusion of ANP had no effect on mean arterial pressure in LE and DI groups. In summary, infusion of ANP in the DI rat resulted in a significant natriuresis, albeit less than in LE rats. The natriuresis in the LE rats occurred despite no significant change in Uosm. These data suggest that mechanisms other than medullary washout are responsible for the natriuretic effects of ANP.

Animals↗
PubMed1988

Effect of meclofenamate on lithium excretion in response to changes in renal perfusion pressure.

Previous studies in dogs have demonstrated that inhibition of prostaglandin synthesis markedly impairs the ability of the kidney to alter sodium excretion in response to changes in renal perfusion pressure (RPP). The objectives of the present study were to determine whether renal prostaglandins play a role in the urinary sodium excretory response to alterations in RPP in the rat and to determine the role of the proximal tubule in this response. RPP was changed from 127 to 109 mm Hg and then to 91 mm Hg with a servo-controlled cuff on the abdominal aorta. Fractional lithium excretion (FELi) was used as an index of ractional sodium reabsorption by the proximal tubule. As a function of increases in RPP, FELi increased, suggesting that fractional sodium reabsorption by the proximal tubule was decreased in response to increases in RPP in control animals. In meclofenamate-treated rats, increases in fractional sodium excretion and FELi in response to increases in RPP were attenuated compared with levels in control animals. The blunted response of FELi in meclofenamate-treated rats suggests that the attenuated increase in urinary sodium excretion observed during increases in RPP reflects an increase in proximal sodium reabsorption mediated by blockade of renal prostaglandins.

Animals↗
PubMed1987

Role of atrial natriuretic factor in the natriuresis of acute volume expansion.

The quantitative role of atrial natriuretic factor (ANF) in mediating the natriuresis induced by acute volume loading was determined in these studies. Plasma level of ANF (PANF), glomerular filtration rate (GFR), and renal excretory responses were measured in three groups of anesthetized Sprague-Dawley rats. In one group of rats (n = 8), acute volume expansion was established by intravenous infusion of saline (5% body wt) over a period of 30 min. A second group of rats (n = 13) was infused with synthetic ANF (2 micrograms X kg-1 X h-1 iv) to mimic the high PANF observed during acute volume loading. A third group (n = 13) served as control. PANF was similar and significantly elevated (P less than 0.05) in volume-expanded and ANF-infused groups compared with control. In control rats, PANF measured 122.0 +/- 12.1 pg/ml, whereas it averaged 389.4 +/- 30.3 pg/ml for volume-expanded and 368.1 +/- 22.3 pg/ml for ANF-infused rats. GFR was also comparable and significantly increased (P less than 0.05) in volume-expanded and ANF-infused groups compared with control rats. Infusion of ANF at a dose to mimic PANF obtained during acute volume expansion resulted in a fourfold increase in the fractional excretion of sodium. The results of these studies suggest that ANF may play an important quantitative role in promoting natriuresis during acute volume expansion.

Animals↗
PubMed1987

Calcitonin inhibits Na+ gradient-dependent phosphate uptake across renal brush-border membranes.

This study was undertaken to determine whether calcitonin inhibits Na+-(Pi) cotransport across luminal brush-border membrane (BBM) of proximal tubules. Further, we determined the relative inhibitions of inorganic phosphate (Pi) transport in BBM vesicles (BBMV) derived from superficial cortical tissue (BBMV-SC) and juxtamedullary tissue (BBMV-JM). The effects of maximally phosphaturic doses of calcitonin were compared with those of parathyroid hormone (PTH). Experiments were performed in acutely thyroparathyroidectomized (TPTX) rats fed either normal (NPD, 0.7%) or low (LPD, 0.07%) Pi diets. After measurement of the fractional excretion of phosphate (FEPi) by clearance, the BBMV-SC and BBMV-JM were prepared from kidneys of the same animals and uptakes of 32Pi were determined. Both calcitonin and PTH inhibited BBMV transport of Pi to a greater degree in BBMV-JM than in BBMV-SC, in rats fed NPD or LPD. Kinetic analysis shows that administration of calcitonin resulted in marked decrease of apparent Vmax for Pi without any changes in apparent Km for Pi. However, in spite of a decreased capacity for Na+ gradient-dependent 32Pi uptake in BBMV-JM and much lesser in BBMV-SC in response to administration of calcitonin and PTH in Pi-deprived rats, these phosphaturic peptides did not increase FEPi. We conclude that calcitonin administration decreases the capacity for Na+-Pi cotransport across BBM in proximal tubules of the acutely TPTX rat.

Animals↗
PubMed1987

Effects of adenosine infusion into renal interstitium on renal hemodynamics.

This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. Infusion of adenosine (bolus 0.5 mumol plus 0.1 mumol/min) decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 (mean +/- SE) to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), (bolus 10 nmol plus 2 nmol/min) decreased GFR from 0.73 +/- 0.07 to 0.21 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, [3H]NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. We conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine.

2-Chloroadenosine↗