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F G Knox

Publications and source records attributed to F G Knox.

At least 73 records · Page 4Linked to original sources
PubMed1990

Mechanism of prostaglandin E2-induced increase of proximal sodium reabsorption in the rat.

Prostaglandin E2, when infused directly into the renal interstitium, enhances sodium reabsorption by the superficial proximal convoluted tubules of anesthetized Sprague-Dawley rats. The present study was designed to investigate the role of angiotensin II in the prostaglandin E2-induced stimulation of proximal sodium reabsorption. Micropuncture at the superficial late proximal tubule demonstrated a significant increase in the fractional reabsorption of sodium from 39.9 +/- 2.3% in control conditions to 51.8 +/- 3.0% (n = 9, P less than 0.01) during the renal interstitial infusion of prostaglandin E2. The stimulatory effect of prostaglandin E2 on proximal sodium reabsorption was markedly attenuated by pretreatment with saralasin. During intravenous saralasin infusion, prostaglandin E2 did not significantly change the fractional reabsorption of sodium from 42.2 +/- 5.8 to 45.4 +/- 6.0% (n = 7, NS). In summary, the stimulatory effect of renal interstitial infusion of prostaglandin E2 on proximal sodium reabsorption was attenuated by pretreatment with saralasin. Therefore renal interstitial infusion of prostaglandin E2 may enhance proximal sodium reabsorption, at least in part, through stimulation of angiotensin II production in the rat kidney.

Absorption↗
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

Response of superficial proximal convoluted tubule to decreased and increased renal perfusion pressure. In vivo microperfusion study in rats.

Although urinary sodium excretion is positively influenced by acute changes in renal perfusion pressure, micropuncture studies show highly conflicting results concerning the response of superficial proximal tubule sodium reabsorption to changes in renal perfusion pressure. In the present study, the changes of superficial proximal reabsorption to decreased and increased renal perfusion pressure were determined in rats by an in vivo microperfusion method. In vivo microperfusion was selected as the method to determine the proximal sodium reabsorption because this method made it possible to deliver a constant fluid and electrolyte load to the proximal tubule without the influence of possible changes of glomerular filtration rate. Renal perfusion pressure was decreased from normal pressure by inflating a suprarenal aortic cuff and was increased from the normal level by the occlusion of celiac and mesenteric arteries and the infrarenal aorta. Although fractional excretion of sodium (FENa) in the urine was decreased from 1.24 +/- 0.23% to 0.45 +/- 0.11% (n = 7, p less than 0.01) when renal perfusion pressure was decreased from 125 +/- 6 to 99 +/- 3 mm Hg, absolute tubular reabsorption by the superficial proximal convoluted tubules was not increased (from 4.4 +/- 0.5 to 4.2 +/- 0.3 nl/min/mm, n = 22). When the renal perfusion pressure was elevated from 126 +/- 4 to 149 +/- 4 mm Hg, tubular reabsorption by the superficial proximal tubules was decreased from 4.1 +/- 0.3 to 2.5 +/- 0.3 nl/min/mm (n = 36, p less than 0.01) with an accompanying increase in FENa (from 1.28 +/- 0.24% to 2.29 +/- 0.37%, n = 9, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
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↗
PubMed1989

Intrarenal mechanisms that regulate sodium excretion in relationship to changes in blood pressure.

Because pressure-related natriuresis may be central to the regulatory role of the kidney on blood pressure, it is important to understand the relationship of humoral systems involved in the control of renal hemodynamics and tubular function. The preglomerular endothelial synthesis of prostaglandin I2 and endothelium-derived relaxing factor seem to modulate autoregulatory control by the afferent arterioles and the release of renin by the juxtaglomerular apparatus. The release of renin is followed by an increase in angiotensin II in the renal interstitium, which is responsible for adjusting the vascular tone of the efferent arterioles and vasa recta and for stimulating proximal tubular reabsorption of sodium. Variations in medullary circulation induced by angiotensin II could alter medullary interstitial pressure and the medullary production of prostaglandins E2 and I2 and, ultimately, could modulate sodium reabsorption in the medullary thick ascending limbs and the collecting ducts.

Blood Pressure↗
PubMed1989

Alterations in blood pressure by derangement of the mechanisms that regulate sodium excretion.

Understanding the sequence of events responsible for pressure-related natriuresis and their pathophysiologic alterations may be useful in distinguishing various types of essential hypertension of renal origin. The perturbation of a distal step in the sequence is likely to be reflected in a simple physiologic defect. For instance, pathophysiologic alterations in the medullary production of prostaglandin E2 might directly influence natriuresis and diuresis because of its modulatory effect on tubular reabsorption of sodium and water. Perturbation of more proximal steps in the sequence could influence all the distal events as well. For instance, prostaglandin I2 and endothelium-derived relaxing factor may be produced by the preglomerular vasculature in response to alterations in renal perfusion pressure and may modulate the release of renin from the juxtaglomerular cells. Thus, variations in the production of prostaglandin I2 or endothelium-derived relaxing factor may be reflected by various renal vascular, tubular, and systemic homeostatic events related to the renin-angiotensin system.

Animals↗
PubMed1989

Proximal tubule response in aldosterone escape.

The response of the proximal tubule to chronic aldosterone administration (15 micrograms.kg-1.day-1) was evaluated in eight conscious female mongrel dogs. Temporal profiles between hemodynamic and hormonal changes and the fractional excretions of sodium and lithium were established. Aldosterone infusion resulted in a significant decrease in urinary sodium excretion from 9.2 +/- 1.3 to 5.8 +/- 0.9 meq/h after 1 day, returning to normal by the 5th day. These changes in urinary sodium excretion were associated with significant elevations of the mean arterial pressure (MAP) from 105 +/- 5 to 111 +/- 6 mmHg and plasma atrial natriuretic factor concentrations (ANF) from 30 +/- 2 to 57 +/- 7 pg/ml beginning the 1st day of infusion. Plasma renin activity (PRA), on the other hand, was depressed by aldosterone, falling below the level of detectability. The fractional excretion of lithium increased significantly by day 2 of aldosterone infusion (from 29 +/- 3 to 44 +/- 6%), reflecting the proximal tubular response to the above changes. We conclude that the proximal tubule responds to increases in MAP and ANF and decreases in PRA during aldosterone infusion by decreasing sodium reabsorption. Subsequent nephron segments must also respond to the volume expansion produced by aldosterone, since the sustained proximal tubule natriuretic response is insufficient to explain all of escape.

Aldosterone↗
PubMed1989

Effect of renal decapsulation on renal interstitial hydrostatic pressure and natriuresis.

The objective of this study was to investigate the possible causal role of renal interstitial hydrostatic pressure (RIHP) in the natriuretic and diuretic responses of the Wistar rat. The relationship between renal perfusion pressure (RPP), RIHP, and fractional excretion of sodium (FENa) was established in the acutely decapsulated kidney and the contralateral control kidney of the same rat. The renal response to acute saline volume expansion was also studied in control and decapsulated kidney. When RPP was allowed to increase from 100 +/- 1.2 to 123 +/- 1.3 mmHg in male Wistar rats (n = 10), RIHP and FENa increased significantly from 3.3 +/- 0.4 mmHg and 0.57 +/- 0.15% to 4.3 +/- 0.4 mmHg and 1.77 +/- 0.41% in the decapsulated kidney and from 4.1 +/- 0.4 mmHg and 0.86 +/- 0.17% to 6.9 +/- 0.5 mmHg and 2.56 +/- 0.38% in control kidney. During saline volume expansion, RIHP and FENa increased significantly from 6.3 +/- 0.5 mmHg and 1.30 +/- 0.43% to 9.8 +/- 0.5 mmHg and 7.53 +/- 0.88% in the decapsulated kidney. In the control kidney, RIHP and FENa were 8.3 +/- 0.6 mmHg and 1.81 +/- 0.35% during control period and increased significantly to 12.7 +/- 0.4 mmHg and 9.31 +/- 0.50% during acute saline volume expansion. We conclude that the renal capsule is essential for the full increase in RIHP and for the full expression of the natriuretic and diuretic responses of pressure natriuresis and acute volume expansion of Wistar rats.

Animals↗
PubMed1989

Effect of renal perfusion pressure on renal interstitial hydrostatic pressure in rats.

The purpose of this study was to investigate the hypothesis that changes in renal perfusion pressure may be transmitted to the renal interstitium and cause alterations in renal interstitial hydrostatic pressure and sodium excretion. A method that utilizes a chronically implanted polyethylene matrix that allows for direct continuous measurement of renal interstitial hydrostatic pressure, and agrees well with subcapsular measurement in rats, was developed. Renal interstitial hydrostatic pressure, fractional excretion of sodium, and urine flow rate were 3.0 +/- 0.3 mmHg, 0.35 +/- 0.13%, and 19.44 +/- 3.00 microliter/min, respectively, when renal perfusion pressure was 101 +/- 0.8 mmHg. When renal perfusion pressure was increased to 123 +/- 0.9 mmHg renal interstitial hydrostatic pressure, fractional excretion of sodium, and urine flow rate increased significantly to 5.8 +/- 0.6 mmHg, 1.29 +/- 0.29%, and 50.76 +/- 8.83 microliter/min, respectively, in anesthetized male Sprague-Dawley rats. These changes occur despite a well-autoregulated glomerular filtration rate and renal blood flow. In conclusion, increasing renal perfusion pressure caused a significant increase in renal interstitial hydrostatic pressure as measured directly by the implanted polyethylene matrix method and was associated with a significant increase in sodium excretion.

Animals↗
PubMed1989

Effect of renal interstitial infusion of arachidonic acid on proximal sodium reabsorption.

The effect of prostaglandins (PGs) on proximal sodium reabsorption has not been fully defined. The objective of the present study was to determine the response of proximal tubular sodium reabsorption to infusions of arachidonic acid and specific PGs into the renal interstitium in rats. Renal interstitial infusions of arachidonic acid as well as the individual PGs, I2, E2, and F2 alpha, were employed to elevate the concentration of these PGs in the kidney. Infusion of 10(-4) M arachidonic acid elicited a marked increase of urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2) from 260.1 +/- 52.7 to 507.4 +/- 129.5 pg/min (P less than 0.05) and a smaller increase of PGE2 from 18.4 +/- 11.2 to 25.9 +/- 10.9 pg/min (P less than 0.05). When micropuncture samples were obtained from superficial late proximal tubules, infusion of arachidonic acid increased the fractional delivery of sodium (FDNa) from 47.8 +/- 5.9 to 58.3 +/- 4.6% (n = 6, P less than 0.01). In the presence of indomethacin, arachidonic acid failed to augment FDNa. Infusion of 10(-5) M PGI2 also increased FDNa from 51.4 +/- 3.4 to 64.0 +/- 4.4% (n = 10, P less than 0.01). PGF2 alpha did not change FDNa and PGE2 decreased it from 53.1 +/- 5.4 to 37.4 +/- 3.3% (n = 8, P less than 0.01). In summary, the present study demonstrates that renal interstitial infusion of arachidonic acid decreases sodium reabsorption by the superficial proximal tubules possibly through the stimulation of PGI2 production.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effect of acute renal decapsulation on pressure natriuresis in SHR and WKY rats.

The objective of these experiments was to study pressure natriuresis in the Wistar-Kyoto (WKY) and the spontaneously hypertensive rat (SHR) during acute bilateral renal decapsulation, a maneuver that partially blocks the increase in renal interstitial hydrostatic pressure (RIHP). In control WKY rats (n = 7), at renal perfusion pressure (RPP) of 105 +/- 0.7 and 125 +/- 1.1 mmHg, RIHP increased from 4.4 +/- 0.4 to 7.2 +/- 0.7 mmHg (P less than 0.05) and fractional excretion of sodium (FENa) increased from 0.23 +/- 0.05 to 1.32 +/- 0.14% (P less than 0.05). Acute bilateral renal decapsulation (n = 6) blunted the increase in RIHP observed when RPP was increased in control WKY rats and abolished the pressure natriuretic and diuretic response. When RPP was allowed to increase from 106 +/- 0.8 to 130 +/- 2.2 mmHg in the WKY rats with decapsulated kidneys, RIHP increased from 3.8 +/- 0.5 to 4.3 +/- 0.4 mmHg but FENa did not significantly change (0.31 +/- 0.12 to 0.43 +/- 0.13%). In control SHRs (n = 7), at RPPs of 135 +/- 0.8 and 163 +/- 3.0 mmHg, RIHP was 4.4 +/- 0.4 and 5.0 +/- 0.6 mmHg (NS) and FENa was 0.41 +/- 0.10 and 0.82 +/- 0.17% (P less than 0.05). Renal decapsulation in the SHR did not affect the blunted relationships between RPP, RIHP, and FENa; at RPPs of 135 +/- 0.3 and 162 +/- 2.9 mmHg (n = 7), RIHP was 4.4 +/- 0.6 and 4.7 +/- 0.5 mmHg (NS) and FENa was 0.43 +/- 0.10 and 0.95 +/- 0.22% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Blunted pressure natriuresis in the Brattleboro diabetes insipidus rat.

Antidiuretic hormone is known to stimulate the renal synthesis of prostaglandins. These autacoids, in turn, modulate the pressure natriuresis phenomenon. Accordingly, the present study was done to test the hypothesis that, in the absence of antidiuretic hormone and antidiuretic hormone-dependent prostaglandin synthesis, the pressure natriuresis response is blunted. Experiments were performed on Brattleboro diabetes insipidus rats (n = 7) and Long Evans control rats (n = 14). A change in perfusion pressure in the Long Evans rats from 89.3 +/- 1.0 to 108.7 +/- 1.1 mm Hg (p less than 0.05) was associated with significant increases in the fractional excretion of sodium (1.1 +/- 0.2 to 2.3 +/- 0.3%) and the urinary prostaglandin excretion (32.6 +/- 6.8 to 56.6 +/- 10.0 pg/min). In contrast, a similar change in perfusion pressure in the diabetes insipidus rat from 88.6 +/- 1.4 to 106.2 +/- 1.5 mm Hg (p less than 0.05) resulted in no significant increases in either sodium or prostaglandin excretions. Treatment of a third group of diabetes insipidus rats (n = 9) with 1-desamino-8-D-arginine vasopressin (1 microgram/day) restored the natriuretic response to increases in renal perfusion pressure. Treated diabetes insipidus and Long Evans control rats had comparable natriuretic responses to increases in renal perfusion pressure. Untreated diabetes insipidus rats, on the other hand, had blunted responses. In summary, the pressure natriuresis response in diabetes insipidus rats is blunted compared with Long Evans control rats. We conclude that antidiuretic hormone is necessary for the complete expression of the pressure natriuresis response.

Animals↗
PubMed1989

Role of prostaglandins in proximal tubule sodium reabsorption: response to elevated renal interstitial hydrostatic pressure.

Previous studies have shown that the elevation of renal interstitial hydrostatic pressure by the direct expansion of renal interstitial volume increases urinary sodium excretion. The objective of the present study was to investigate whether proximal tubules respond to the elevated renal interstitial hydrostatic pressure and whether the inhibition of prostaglandin synthesis would alter the effect of elevated renal interstitial hydrostatic pressure on proximal sodium reabsorption. Expansion of renal interstitial volume by injecting 100 microliters of 2.5% albumin solution through a chronically implanted matrix increased renal interstitial hydrostatic pressure similarly in control rats (n = 8) and in indomethacin (n = 8) or meclofenamate-treated (n = 7) rats. In the absence of prostaglandin synthesis inhibition, renal interstitial volume expansion significantly increased the fractional delivery of sodium at the superficial late proximal tubules from 56.5 +/- 6.1 to 67.0 +/- 6.5% (p less than 0.01) with an accompanying increase in fractional excretion of sodium from 2.1 +/- 0.5 to 3.0 +/- 0.4% (p less than 0.01). In the presence of indomethacin or meclofenamate, renal interstitial volume expansion failed to augment the fractional delivery of sodium and the fractional excretion of sodium. In summary, these studies demonstrate that the synthesis of prostaglandins plays a role in the regulation of sodium reabsorption by the proximal tubules in response to elevated renal interstitial hydrostatic pressure.

Animals↗