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Biomedical subjects

F G Knox

Publications and source records attributed to F G Knox.

At least 127 records · Page 7Linked to original sources
PubMed1984

Mechanism of natriuresis during intrarenal infusion of prostaglandins.

Intrarenal infusion of the natural prostaglandin PGE2 increases renal blood flow, renal interstitial hydrostatic pressure, and urinary sodium excretion. A newly synthesized prostaglandin analogue, 4-3-[3-[2-(1-hydroxycyclohexyl)- ethyl]-4-oxo-2-thiazolidinyl]propyl benzoic acid, increases renal blood flow without increasing sodium excretion. To investigate the role of renal interstitial hydrostatic pressure in this dissociation, comparisons were made between PGE2 and the prostaglandin analogue. Intrarenal infusion of PGE2 increased renal blood flow, renal interstitial hydrostatic pressure, and urinary sodium excretion. Following a similar increase in renal blood flow with intrarenal infusion of prostaglandin analogue, renal interstitial hydrostatic pressure and urinary sodium excretion were not changed. To determine whether increases in urinary sodium excretion due to PGE2 infusion are causally related to the increase in renal interstitial hydrostatic pressure rather than to the increase in renal blood flow, responses to PGE2 were obtained in the absence of increases in interstitial pressure. When renal interstitial hydrostatic pressure was held constant, urinary sodium excretion did not change although there was a marked increase in renal blood flow. We conclude that increased renal interstitial hydrostatic pressure is necessary to produce an increase in urinary sodium excretion with prostaglandin-mediated renal vasodilation.

Animals↗
PubMed1984

Failure of angiotensin II to reduce plasma renin activity in hypertensive pregnant women.

The hypothesis that pregnancy induced hypertension (PIH) is associated with abnormal physiological control of plasma renin activity (PRA) was tested by studying the effects of graded infusion of angiotensin II (ANG II) on PRA, plasma aldosterone (PA), and blood pressure in normal pregnancy, PIH, non-pregnant women in luteal and follicular phase of the menstrual cycle, and males. PIH occurring in the second trimester was associated with elevated PRA, PA and blood pressure compared with all other groups, and reduced urinary thromboxane excretion compared with normal pregnancy. Exogenous ANG II infusion failed to suppress existing PRA in patients with PIH, in contrast to all other groups, but increased PA in all groups. It is concluded that PIH occurring in the second trimester is associated with elevated PRA, PA and blood pressure. The inability of circulating ANG II to reduce PRA in PIH may constitute a major alteration underlying the pathophysiology of PIH.

Adult↗
PubMed1983

Intrarenal blood flow distribution during adenosine-mediated vasoconstriction.

Intrarenal infusion of adenosine induces an initial vasoconstriction followed by a subsequent vasodilation. The intrarenal distribution of blood flow in the vasoconstriction phase is unknown. The present study was undertaken to assess the effect of intrarenal infusion of adenosine on intracortical distribution of renal blood flow during both the vasoconstriction and vasodilation phases. Renal blood flow distribution was measured with radiolabeled microspheres in anesthetized sodium-depleted dogs before and during the early vasoconstriction phase and the late vasodilation phase of intrarenal infusion of adenosine. During the vasoconstriction phase, there was a uniform decrease in blood flow in each renal cortical zone. In the late phase of adenosine infusion, there was a significant increase in deep cortical flow without significant changes in superficial cortical flow compared with control. The effects of adenosine were also compared with those exerted by norepinephrine in which decreased blood flow was demonstrated in all zones. We conclude that the vasoconstrictor phase of adenosine infusion is characterized by a uniform reduction of renal blood flow to all cortical zones, whereas the vasodilator phase is characterized by a selective deep cortical vasodilation.

Adenosine↗
PubMed1983

Tubular capacity of phosphate transport in phosphate-deprived rats: effects of nicotinamide and PTH.

The present study tested the hypothesis that nicotinamide and/or parathyroid hormone (PTH) would reverse the resistance of phosphate-deprived rats to the phosphaturic effects of phosphate infusions by reducing the tubular capacity for phosphate transport. The response to progressively increasing rates of phosphate infusion (1, 2, and 3 mumol/min) was evaluated in thyroparathyroidectomized (TPTX) rats fed low phosphate diet (0.07%) for 4 days and treated with either vehicle or nicotinamide 2 h before the experiment. Following phosphate infusions, phosphate excretion was unchanged in vehicle-treated rats but increased progressively in nicotinamide-treated rats to 60% of the final rate of infusion. In a second series conducted in the presence of exogenous PTH, vehicle-treated rats responded to phosphate infusions by increasing phosphate excretion to 80-90% of the rate of infusion. In the presence of both nicotinamide and PTH, the rate of phosphate excretion matched the rate of infusion. Vehicle-treated rats displayed the highest reabsorptive rates without reaching a transport maximum, whereas a lower maximum reabsorptive rate was evident in nicotinamide-treated rats. However, in both groups given PTH, not only was the transport maximum lower but it declined with further increases in filtered load. We conclude that nicotinamide and PTH reverse the effects of dietary phosphate deprivation by decreasing the tubular capacity for phosphate transport.

Animals↗
PubMed1983

Adaptation of deep and superficial nephrons to changes in dietary phosphate intake.

Dietary phosphate intake is now recognized to be a primary regulator of renal phosphate excretion. However, the nephron sites involved in the adaptation to changes in dietary phosphate are unclear. We tested the hypothesis that deep and superficial nephrons respond differently to changes in dietary phosphate by comparing fractional phosphate delivery (FDP%) from proximal tubules of both nephron populations. Because phosphate reabsorption is not detectable in the ascending loop of Henle, FDP% to the superficial early distal tubule and papillary loop of Henle reflect delivery from superficial and deep nephron proximal tubules, respectively. Micropuncture experiments were performed in 17 acutely TPTX rats fed either a low (0.07%) or a high (1.8%) phosphate diet for 4 days prior to the experiment. In low phosphate diet, fractional phosphate excretion was 0.93 +/- 0.26%. FDP% was 7.5 +/- 0.5 and 9.1 +/- 2.2% from superficial and deep nephron proximal tubules, respectively (P greater than 0.05). In high phosphate diet, fractional phosphate excretion was 29.6 +/- 5.0%. FDP% was significantly greater from superficial proximal tubules, 33.9 +/- 4.6%, compared with that from deep nephron proximal tubules, 14.0 +/- 2.7% (P less than 0.05). We conclude that significant adaptation of phosphate reabsorption in response to changes in dietary phosphate intake occurs in the superficial but not in the deep nephron proximal tubule in acutely TPTX volume-expanded rats. In addition, the presence of distal phosphate reabsorption was not evident in high phosphate diet but must occur in low phosphate diet.

Animals↗
PubMed1983

Glomerular filtration dynamics during renal vasodilation with acetylcholine in the dog.

The reason for the failure of glomerular filtration rate (GFR) to exhibit plasma flow dependency during pharmacologic vasodilation remains unclear although it has been suggested on the basis of experiments in rats that vasodilators may lead to a reduction in the glomerular filtration coefficient (Kf). To evaluate the applicability of this hypothesis to the dog, the effects of vasodilation with acetylcholine on glomerular dynamics and Kf were evaluated in two groups of dogs. One group (n = 19) was studied at spontaneous arterial pressures to allow maximum vasodilation to occur. In the other group (n = 5), renal arterial pressure was reduced and maintained at approximately 89 mmHg. Glomerular filtration rate and single nephron glomerular filtration rate were not altered significantly during acetylcholine infusion in either of the two groups. Both whole kidney and superficial filtration fractions decreased significantly. At spontaneous arterial pressures, transglomerular hydrostatic pressure was not altered significantly because of equivalent increases in proximal tubule pressure and in glomerular pressure. In the dogs studied at reduced renal perfusion pressure, glomerular capillary pressure did not change, but proximal tubule pressure increased slightly. Average effective filtration pressures and Kf were not significantly altered during the infusion of acetylcholine either at spontaneous or reduced renal perfusion pressures. These observations indicate that Kf in the dog is not significantly decreased by acetylcholine and that GFR is not affected during infusion of this agent because the effective filtration pressure is not significantly altered.

Acetylcholine↗
PubMed1983

Calcitonin decreases the renal tubular capacity for phosphate reabsorption.

The effects of pharmacologic doses of synthetic salmon calcitonin on the renal tubular capacity of phosphate (Pi) transport were determined in the presence and absence of maximally phosphaturic doses of parathyroid hormone (PTH). Thyroparathyroidectomized rats were given graded infusions of Pi (1, 2, and 3 mumol/min) to prevent the hypophosphatemic effects of calcitonin and to determine the maximum transport of Pi for the kidney (TmPi/GFR). The maximum transport of Pi for the rats treated with calcitonin was 2.46 +/- 0.27 mumol/ml. This value was significantly less than that of 3.88 +/- 0.32 mumol/ml (P less than 0.05) for the control animals but was significantly greater than the maximum transport of Pi of 1.16 +/- 0.05 mumol/ml (P less than 0.05) for the rats treated with PTH. Furthermore, there was no significant difference between the maximum transport of Pi for the rats treated with PTH and that of 1.04 +/- 0.05 mumol/ml for the rats treated with PTH plus calcitonin. We conclude that pharmacologic doses of calcitonin decrease the tubular capacity for Pi reabsorption of the kidney and that the effect is significantly smaller than that of maximally phosphaturic doses of PTH.

Absorption↗
PubMed1983

Role of hydrostatic and oncotic pressures in renal sodium reabsorption.

Physical factors, and renal interstitial hydrostatic pressure in particular, have an important effect on sodium excretion by the kidney. Changes in hydrostatic and oncotic pressures in the peritubular microcirculation may have effects on proximal tubule reabsorption under some, but not all, circumstances. In regard to control of sodium excretion, the loop of Henle may be a particularly important segment which is sensitive to transepithelial hydrostatic pressure changes. There is little evidence to support an effect of physical factors on sodium reabsorption by the distal tubule. The collecting tubule may be another pressure-sensitive site; however, changes in sodium reabsorption by deep nephrons in the kidney may account for changes that have been attributed to the collecting duct. Changes in intrarenal pressure may be an important link in the regulation of sodium excretion, particularly in pathological circumstances, such as the exaggerated natriuresis of hypertension and the sodium retention seen in congestive heart failure.

Absorption↗
PubMed1983

Effects of secretin on peritubular capillary physical factors and proximal fluid reabsorption in the rat.

The effects of secretin vasodilation on peritubular capillary Starling forces and absolute proximal reabsorption were examined in the rat. Secretin was infused at 75 mU/kg per min into the aorta above the left renal artery. Efferent plasma flow increased from 125 +/- 28 to 230 +/- 40 nl/min with secretin infusion. Single nephron filtration rate (44 +/- 6 vs. 44 +/- 7 nl/min) and absolute proximal reabsorption (21 +/- 5 vs. 21 +/- 4 nl/min) were not significantly changed. Peritubular capillary and interstitial hydrostatic pressures increased with secretin infusions (from 9 +/- 0.4 to 15 +/- 0.7 mmHg and from 3 +/- 0.2 to 4 +/- 0.2 mmHg, respectively). Both peritubular capillary and interstitial oncotic pressures decreased (from 25 +/- 2 to 20 +/- 2 mmHg and from 10 +/- 1 to 4 +/- 1 mmHg, respectively) during secretin infusion. The net reabsorption pressure for peritubular capillary uptake significantly decreased from 9 +/- 2 to 5 +/- 2 mmHg and the coefficient of reabsorption increased from 3 +/- 1 to 6 +/- 2 nl/min per mmHg. We conclude that although secretin causes a vasodilation and decreases net reabsorption pressure, absolute proximal reabsorption is unchanged. Peritubular capillary uptake is maintained, and since net reabsorption pressure is decreased, the coefficient of reabsorption is increased.

Absorption↗
PubMed1983

Restoration of phosphaturia in phosphate-deprived rats in the presence of both parathyroid hormone and phosphate infusion.

The present study tested the hypothesis that the combination of parathyroid hormone and phosphate infusion would be phosphaturic in phosphate-deprived rats. Clearance experiments were performed in Sprague-Dawley rats fed a low-phosphate diet for 4 days. The animals were first given a phosphate infusion and then administered parathyroid hormone. The reverse experiment was also performed in a second group of rats by giving the hormone first followed by a phosphate infusion. There was no increase in phosphate excretion in response to phosphate infusion or parathyroid hormone given alone. However, the combination of parathyroid hormone and phosphate infusions, given in either order, was phosphaturic in phosphate-deprived rats.

Animals↗
PubMed1983

Renal vasoconstrictive response to contrast medium. The role of sodium balance and the renin-angiotensin system.

The injection of contrast medium into the renal artery causes a biphasic change in renal blood flow, a transient vasodilation followed by a more prolonged vasoconstrictive phase. The role of sodium balance in the vasoconstrictive response to contrast medium was evaluated in sodium-deplete dogs (n = 5) and sodium-replete dogs (n = 5). Contrast medium, 2 ml of diatrizoate solution per 4 sec, was injected into the renal artery in anesthetized dogs. Renal blood flow was 117 +/- 25 ml/min and 173 +/- 12 in the sodium-deplete and sodium-replete dogs, respectively. After the injection of contrast medium and following the transient vasodilation phase, renal blood flow significantly decreased from baseline by 42.2% +/- 4.2 and 12.2% +/- 1.1 in sodium-deplete and sodium-replete dogs, respectively. The duration of the vasoconstriction phase was significantly prolonged in the sodium-deplete dogs, 343 +/- 27 sec vs. 147 +/- 48 in sodium-replete dogs. Blockade of the intrarenal renin-angiotensin system with the renal artery infusion of Sar1-Ala8-All (50 micrograms/kg/min) did not significantly alter the magnitude of vasoconstrictive response to contrast medium in sodium-deplete animals; however, the duration of the vasoconstrictive phase was decreased from 277 +/- 59 sec to 86 +/- 13. We conclude that (1) sodium depletion accentuates both the magnitude and duration of the vasoconstrictive phase of the renal blood flow response to injection of contrast medium and (2) blockade of the intrarenal renin-angiotensin system shortens the duration of this response.

Animals↗
PubMed1982

Nicotinamide restores phosphaturic effect of PTH and calcitonin in phosphate deprivation.

Results of previous studies suggest a potentially important role for nicotinamide adenine dinucleotide (NAD) in the cellular regulation of phosphate transport by the renal proximal tubules. The present clearance studies were performed to evaluate whether intraperitoneal administration of nicotinamide, a precursor of NAD and inhibitor of NAD catabolism, would not only increase phosphate excretion but also restore the phosphaturic response to parathyroid hormone (PTH) in rats fed a low phosphate diet. Rats fed a low phosphate diet were resistant to the phosphaturic effect of PTH, calcitonin, and dibutyryl cAMP (DBcAMP) in spite of the fact that all three agents elicited an increase in the urinary excretion of cAMP. Administration of nicotinamide to rats fed a low phosphate diet increased renal cortical NAD levels, increased phosphate excretion, partially restored the phosphaturic effect of PTH and DBcAMP, and completely restored the phosphaturic response to calcitonin. We conclude that nicotinamide restores the phosphaturic effect of PTH and calcitonin in rats fed a low phosphate diet by acting at a cellular step subsequent to cAMP generation to inhibit tubular reabsorption of phosphate.

Animals↗
PubMed1982

Segmental analysis of sodium reabsorption during renal vein constriction.

Clearance and micropuncture studies were performed in rats to identify the nephron site(s) of altered sodium reabsorption during partial renal vein constriction in the presence and absence of volume expansion. Renal vein constriction increased fractional deliver of sodium to the late proximal tubule from 52 +/- 3 to 61 +/- 4% in euvolemia and from 59 +/- 3 to 65 +/- 3% in volume expansion. In euvolemia, fractional delivery of sodium to the early distal tubule was 13 +/- 3% before and 24 +/- 6% after renal vein constriction. In volume expansion, fractional delivery of sodium to the early distal tubule decreased from 15 +/- 3 to 9 +/- 2% in response to renal vein constriction. We conclude that renal vein constriction decreases sodium reabsorption by the proximal tubule both in euvolemia and in volume expansion but that it increases sodium reabsorption by the superficial loop of Henle only in the presence of volume expansion.

Animals↗
PubMed1982

Acetylcholine-induced vasodilation without natriuresis during control of interstitial pressure.

Increased renal blood flow and increased renal interstitial pressure have been proposed as mechanisms for the natriuresis caused by vasodilation with acetylcholine. We tested the hypothesis that the natriuresis due to acetylcholine is associated with the increase in interstitial pressure rather than with the increase in blood flow. Experiments were performed in decapsulated kidneys that, along with partial aortic clamping, allowed dissociation of the increases in renal interstitial pressure and blood flow. At the beginning of intrarenal acetylcholine infusion (2 micrograms . kg-1 . min-1), the aorta was clamped so that a vasodilation occurred without an increase in interstitial pressure. A response to acetylcholine was also obtained when interstitial pressure was allowed to increase. During this response, renal blood flow, interstitial pressure, and fractional sodium excretion increased. During control of interstitial pressure, renal blood flow increased, but fractional sodium excretion did not change. Thus, when interstitial pressure was controlled, the acetylcholine-induced vasodilation did not result in an increase in fractional sodium excretion. These results demonstrate that an increase in renal interstitial pressure is required for the natriuresis associated with acetylcholine-induced vasodilation.

Acetylcholine↗
PubMed1982

Effect of respiratory alkalosis on renal phosphate excretion.

Respiratory alkalosis induced hypophosphatemia and hypophosphaturia in intact animals. The present studies evaluated the effect of respiratory alkalosis on tissue phosphate distribution and renal phosphate transport in the presence and absence of parathyroid hormone (PTH). Respiratory alkalosis decreased plasma phosphate concentration and increased phosphate concentrations in muscle and liver. It decreased fractional phosphate excretion (FEPi) from 6.1 +/- 1.4 to 0.6 +/- 0.2%. In thyroparathyroidectomized (TPTX) rats infused with 20 mM phosphate, respiratory alkalosis decreased FEPi from 15.0 +/- 0.9 to 5.5 +/- 0.1%. PTH or dibutyryl cAMP administration produced a phosphaturia that was blunted by respiratory alkalosis. The phosphaturic response to PTH was also blunted in hypocapnic rats in which alkalosis was prevented by infusion of HCl. We conclude that respiratory alkalosis increases phosphate uptake by muscle, which largely accounts for the hypophosphatemia. The kidney response with increased phosphate reabsorption independent of plasma and kidney phosphate concentrations and with refractoriness to the phosphaturic effect of PTH. This refractoriness to the phosphaturic effect of PTH is due to decreased PCO2 rather than to the concomitant extracellular alkalosis.

Alkalosis, Respiratory↗