Biomedical subjects

F G Knox

Publications and source records attributed to F G Knox.

At least 55 records · Page 3Linked to original sources

PubMed1994

Effect of increased dietary phosphate intake on dopamine excretion in the presence and absence of the renal nerves.

Studies were performed to determine the relative contributions of the renal nerves and tubule synthesis to dopamine excretion during increased dietary phosphate intake. Rats underwent bilateral renal denervation (n = 5) or sham surgery (n = 5) 1 week prior to the initiation of the balance studies. All rats were placed in metabolic cages and fed 12 g/day of a low phosphate diet (LPD, 0.07%, Pi) for 4 days, then high phosphate diet (HPD, 1.8% Pi) for 4 days. Sodium, potassium, and chloride contents were made similar in LPD and HPD by adding sodium chloride and potassium carbonate to the food. Urine samples were collected every 24 h for determination of free dopamine and electrolyte excretions. The mean urinary phosphate excretion for 4 days of LPD was 0.17 +/- 0.11 mmol/day in the group with bilateral renal denervation and 0.18 +/- 0.11 mmol/day in the group with innervated kidneys. Likewise, dopamine excretion was similar in both groups in the absence (2.5 +/- 0.2 microgram/day) and in the presence (2.3 +/- 0.1 microgram/day) of the renal nerves in rats fed LPD. Increasing dietary phosphate intake from 0.07 to 1.8% significantly increased urinary phosphate and dopamine excretions. The mean urinary phosphate excretion for 4 days was similar in the denervated (4.4 +/- 0.9 mmol/day) and innervated (4.1 +/- 0.5 mmol/day) groups. The mean urinary dopamine excretion for the 4 days of HPD significantly increased to 4.5 +/- 0.5 microgram/day in the group with chronic bilateral renal denervation and 3.7 +/- 0.2 microgram/day in the group with innervated kidneys. Plasma 3,4-dihydroxyphenylalanine (DOPA) and dopamine levels were not changed by increased dietary phosphate intake. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Increased plasma level of endothelin-1 in the Okamoto spontaneously hypertensive rat.

The objectives of this study were to determine plasma levels of endothelin (ET) in a genetic model of hypertension and in control rats during control conditions and in response to short-term volume expansion with saline. Okamoto spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats were used in this study. One group of each strain served as control animals, and another group of each strain underwent volume expansion with saline (5% of body weight infused during a period of 30 minutes). The levels of ET-1 and ET-3 were measured in plasma by using a double-antibody radioimmunoassay. In the control groups of SHR and WKY rats, plasma ET-1 levels were 72.5 +/- 14.9 pg/ml (N = 8) and 40.2 +/- 7.5 pg/ml (N = 12), respectively (P < 0.05). In the volume-expanded SHR group (N = 8), the plasma ET-1 level was 45.5 +/- 11.1 pg/ml (approximately 37% less than that of the control SHR group), whereas it was 40.6 +/- 10.2 pg/ml in the volume-expanded group of WKY rats (N = 10) (almost identical to that of the control WKY group). Plasma levels of ET-3 were similar in control and in volume-expanded groups of SHR and WKY rats. These data show that basal levels of plasma ET-1 are significantly higher in the SHR than in the WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Catecholamines and phosphate excretion by the remnant kidney.

The remnant kidney (RK) exhibits an enhanced fractional excretion of phosphate (FEPi) even in the absence of parathyroid hormone (PTH). Thus, factors other than PTH contribute to this adaptive phosphaturia. Dopamine (DA) infusion is phosphaturic, whereas stimulation of adrenoreceptors is antiphosphaturic. Therefore, the hypothesis that alterations in catecholamines by the RK may be associated with the phosphaturia exhibited by this model was tested. Male Sprague-Dawley rats were subjected to right nephrectomy and surgical ablation of the left renal poles. Four weeks later rats with a RK (N = 10) and control rats with intact kidneys (N = 9) were anesthetized and thyroparathyroidectomized (TPTX). Two hours after TPTX, urine samples were collected for measurements of urinary free DA excretion. Subsequently, 3% inulin in saline was infused for one hour and a 30 minute clearance was taken. The kidneys were then removed and frozen for determination of tissue norepinephrine (NE) and DA concentrations. Glomerular filtration rate was significantly lower in rats with a RK than in controls (0.57 +/- 0.07 vs. 0.83 +/- 0.08 ml/min/g kidney wt), whereas fractional excretion of phosphate (FEPi) was significantly higher (29.4 +/- 4.7 vs. 8.3 +/- 3.4%). Tissue NE concentration was significantly lower in the RK than in the control intact kidney (85.10 +/- 4.95 vs. 129.60 +/- 7.20 ng/g), whereas urinary DA excretion per nephron was significantly higher in the RK (0.12 +/- 0.02 vs. 0.04 +/- 0.006 pg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Role of renal interstitial hydrostatic pressure in natriuresis of systemic nitric oxide inhibition.

Systemic inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) increases renal perfusion pressure (RPP) and urinary sodium excretion. Increased RPP has been proposed as one of the mechanisms for the natriuresis caused by intravenous infusion of L-NMMA. We tested the hypothesis that increases in renal interstitial hydrostatic pressure (RIHP) are required for the natriuresis of L-NMMA infusion. Experiments were performed in four groups of Sprague-Dawley rats in which partial aortic clamping and/or bilateral renal decapsulation was performed to control RPP and RIHP. Infusion of L-NMMA (15 mg/kg bolus + 500 micrograms.kg-1 x min-1 continuous infusion) increased RPP (delta+ 14 +/- 1 mmHg), RIHP (delta+ 3.6 +/- 0.7 mmHg), and fractional excretion of sodium (FENa; delta 2.4 +/- 0.6%, P < 0.005). When RPP was prevented from increasing by controlling RPP with an adjustable clamp around the suprarenal aorta, RIHP and FENa did not significantly change. When only RIHP was held constant by bilateral renal decapsulation, FENa was not significantly increased (delta+ 0.68 +/- 0.36%, not significant), despite a significant rise in RPP (delta+ 18 +/- 2 mmHg, P < 0.001). Control of both RPP and RIHP prevented the increase in FENa. Thus, when renal interstitial pressure was controlled, the infusion of L-NMMA did not result in an increase in FENa. These results demonstrate that an increase in RIHP is a necessary component in the natriuresis due to systemic infusion of L-NMMA.

Animals↗

PubMed1993

Autocrine/paracrine regulation of renal Na(+)-phosphate cotransport by dopamine.

We tested the hypothesis that dopamine (DA) acts as an autocrine/paracrine regulator of Na(+)-Pi symport in proximal tubules, using opossum kidney (OK) cells as an in vivo model. Both DA and parathyroid hormone (PTH) increased adenosine 3',5'-cyclic monophosphate (cAMP) and inhibited Na(+)-gradient-dependent uptake of 32P but not that of L-[3H]-alanine. Incubation of OK cells with L-dopa, a DA precursor, resulted in accumulation of DA (7.4 nM), a ninefold increase of cAMP in the medium, and an inhibition (-10%) of Na(+)-Pi uptake. Carbidopa, an inhibitor of aromatic-L-amino acid decarboxylase, prevented the formation of DA from L-dopa, the increase in cAMP, and the inhibition of Na(+)-Pi cotransport. Pi-replete OK cells produced more DA (+15%) from L-dopa than Pi-deprived cells; however, the endogenous DA inhibited Na(+)-Pi cotransport both in Pi-deprived and in Pi-replete cells. Thus OK cells can synthesize DA from L-dopa in a quantity sufficient to elicit both the maximum DA-stimulated cAMP accumulation and inhibition of Na(+)-Pi cotransport in the same cell population. Our data, obtained on an in vitro system, support the hypothesis proposing that DA generated in proximal tubular cells can modulate, via cAMP, the Na(+)-Pi symport in the same or adjacent cells. If present in the kidney, this pathway might represent an autocrine/paracrine system that can contribute to regulation of renal Pi homeostasis.

Alanine↗

PubMed1993

Excretion of catecholamines and metabolites in response to increased dietary phosphate intake.

The urinary excretion of free dopamine, norepinephrine, and epinephrine could reflect the contribution of the neural release and filtration of these catecholamines as well as the intrarenal tubular synthesis and metabolism of dopamine. Because these catecholamines are rapidly metabolized, the excretion of the free amines represents only a fraction of the total release and synthesis by the kidney. The present study determined the effect of increasing dietary phosphate intake on the excretion of free dopamine, norepinephrine, and epinephrine and their primary stable metabolites. Seven male rats were placed in metabolic balance cages and fed 12 gm/day of normal phosphate diet (NPD) (0.7% inorganic phosphorus [Pi]) for 4 days and then fed a high phosphate diet (HPD) (1.8% Pi) for 4 days. Twenty-four-hour urine samples were collected for determination of free catecholamines, their major stable metabolites, and electrolyte excretions. The urinary excretion data for the seven rats was combined for all 4 days of each dietary regimen. Increasing phosphate intake from 0.7% to 1.8% significantly increased free dopamine excretion by 23%, from 5.6 +/- 0.2 to 6.8 +/- 0.1 micrograms/day (n = 7, p < 0.05). This increase in free dopamine excretion was associated with similar increases in urinary excretion of dopamine glucuronide, 21.6 +/- 1.3 to 27.9 +/- 1.8 micrograms/day (32%) and the dopamine metabolite DOPAC, 9.4 +/- 0.5 to 12.1 +/- 0.6 micrograms/day (30%) and total dopamine excretion from 32.9 +/- 1.7 to 41.0 +/- 1.9 micrograms/day (27%). Plasma DOPA levels were unchanged by increased dietary phosphate intake; however, plasma norepinephrine levels decreased significantly. Excretion of free or sulfated norepinephrine was not changed by increased phosphate intake. However, excretion of MHPG, a metabolite of norepinephrine and epinephrine, decreased significantly, from 33.7 +/- 2.1 to 23.9 +/- 0.8 micrograms/day, n = 7, p < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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

Site of restoration of the effect of PTH by propranolol in respiratory alkalosis.

Respiratory alkalosis decreases the phosphaturic response to parathyroid hormone (PTH). beta-adrenoreceptor blockade by propranolol infusion restores the phosphaturic effect of PTH in respiratory alkalotic rats; however, the nephron site of these changes in phosphate reabsorption by propranolol is not known. The present study was performed to localize the nephron segment(s) involved in the restoration of the phosphaturic effect of PTH by propranolol infusion in respiratory alkalotic rats. PTH infusion increased the fractional delivery of phosphate (FDPi) to the late proximal tubule to similar levels in the propranolol and vehicle-infused respiratory alkalotic rats (FDPi 46.6 +/- 4.4% and 48.6 +/- 4.2%, respectively). In contrast, PTH only increased FDPi to the early distal tubules (to 17.1 +/- 0.9%) in the absence of propranolol compared to FDPi 41.9 +/- 2.5% in the presence of propranolol in respiratory alkalotic animals. We conclude that the restoration of the phosphaturic effect of PTH in respiratory alkalotic rats by propranolol infusion is due primarily to decreased reabsorption of phosphate by the straight segment of the proximal tubule.

Alkalosis, Respiratory↗

PubMed1990

Propranolol restores phosphaturic effect of PTH in short-term phosphate deprivation.

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone (PTH). The present study evaluated the role of the beta-adrenergic system in this resistance phenomenon. In clearance experiments performed on acutely thyroparathyroidectomized male Sprague-Dawley rats, the phosphaturic response to PTH was determined in the presence and absence of propranolol in rats fed a low-phosphate diet (LPD) for 0.5, 1, 2, 3, or 4 days. Fractional excretion of phosphate (FEPi) in control rats fed a normal-phosphate diet (NPD) increased from 4.37 +/- 1.6 to 38.5 +/- 3.4% in response to PTH infusion. Propranolol did not change FEPi in NPD animals in the absence or in the presence of PTH (2.0 +/- 1.1 vs. 36.7 +/- 1.6%). LPD resulted in a gradual decrease in the phosphaturic response to PTH infusion as compared with NPD animals. PTH increased FEPi to 24.2 +/- 6.0% after one-half day of LPD, but when the infusion was supplemented with propranolol, PTH increased FEPi to 38.0 +/- 4.7%, similar to that in NPD animals. In the group fed LPD for one day, PTH increased FEPi to 16.9 +/- 4.3%, whereas in the presence of propranolol FEPi was restored to a similar level as in the NPD group (36.0 +/- 5.9%). Two days of LPD markedly decreased FEPi in response to PTH to 7.9 +/- 3.8% as compared with NPD rats, and propranolol infusion did not change this value significantly. Three and 4 days of LPD induced complete resistance to the phosphaturic effect of PTH in the presence as well as in the absence of propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗