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Biomedical subjects

F G Knox

Publications and source records attributed to F G Knox.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of renal interstitial infusion of L-dopa on sodium and phosphate excretions.

It has been hypothesized that dopamine synthesized by the proximal tubule can act as a paracrine substance that regulates reabsorption by the proximal tubule. The present study was performed to study the effects of the stimulation of endogenous synthesis of dopamine by infusion of L-DOPA directly into the renal interstitium on sodium and phosphate excretions and to determine the roles of D1 and D2 receptors in the response. The infusion of L-DOPA (50 microg/kg/min) into the renal interstitium through an implanted matrix significantly increased the fractional excretion of sodium (FENa) from 1.0%+/-0.2% to 3.1%+/-0.6% and the fractional excretion of phosphate (FEPi) from 23%+/-3% to 36%+/-3%, P < .05, n = 10. The infusion of D1 receptor antagonist SCH23390 or SKF83566 (5 microg/kg/min) into the renal interstitium blocked the natriuretic (FENa 1.5%+/-0.2% to 1.9%+/-0.4%) and phosphaturic (FEPi 41%+/-3% to 41%+/-4%) effects of L-DOPA infusion. The infusion of the D2 receptor antagonist sulpiride at a rate of 4 microg/kg/min into the renal interstitium also attenuated the natriuretic (FENa 1.3%+/-0.3% to 1.6%+/-0.5%) and phosphaturic effects of L-DOPA infusion (FEPi 36%+/-5% to 39%+/-5%). We conclude that the renal interstitial infusion of L-DOPA increases sodium and phosphate excretions and that these responses are mediated by D1 and D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Effect of renal interstitial adenosine infusion on phosphate excretion in diabetes mellitus rats.

We previously demonstrated an increased sensitivity of the renal vasculature to adenosine (ADO) mediated via ADO A1 receptors in streptozotocin (STZ) diabetic rats. Because ADO stimulates P(i) reabsorption in the proximal tubule, the present study was performed to determine whether the sensitivity of the renal tubular system to the antiphosphaturic effect of ADO is enhanced in STZ rats. Clearance studies were performed, and ADO was infused into the renal interstitium via implanted matrices in STZ- and control (Con) rats to mimic the effects of endogenous ADO. Renal phosphate excretion was significantly increased in STZ rats (0.75 +/- 0.05 mumol/24 h) compared with Con rats (0.35 +/- 0.08 mumol/24 h), and fractional phosphate excretion (FEPi) tended to be higher in STZ rats (34.8 +/- 4.1%) than in Con rats (26.7 +/- 2.2%). Renal interstitial ADO infusion (5 mumol/h) was significantly more antiphosphaturic in STZ rats (FEPi decreased by 2.90 +/- 1.6%; P > 0.05), in which ADO only tended to decrease FEPi. To determine the role of ADO A1 receptors on P(i) excretion, the selective ADO A1 receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was infused into the renal interstitium. DPCPX increased FEPi by 4.3 +/- 1.2% (P < 0.05) in the presence and 7.1 +/- 3.9% (P < 0.05) in the absence of ADO infusion in Con rats but had no effect on FEPi in STZ rats. In conclusion, STZ-diabetes mellitus enhances the antiphosphaturic effect of ADO by mechanisms unrelated to ADO A1 receptor stimulation.

Adenosine↗
PubMed1998

Effect of volume expansion on the paracellular flux of lanthanum in the proximal tubule.

Although studies of volume expansion (VE) in the Necturus suggest a major role for paracellular flux in reabsorption by the proximal tubule, results from morphologic or electrophysiologic studies of the effect of VE on the rat proximal tubule suggest only a minor role for paracellular transport. In the present study, during in vivo microperfusion, lanthanum was used as an extracellular marker to determine bidirectional paracellular flux in the rat proximal tubule before and during 10% VE. Lanthanum itself did not affect proximal tubule reabsorption (delta 0.7 +/- 3.3 nl/min, LaCl3 versus saline infusion, n = 7). When lanthanum was added to the luminal perfusate, paracellular lanthanum efflux from the lumen to the interstitium was 28.9 +/- 6.6 pg/min per mm, n = 7. Subsequent VE significantly decreased the paracellular lumen-to-interstitium efflux to 12.8 +/- 8.3 pg/min per mm concomitant with a 49% decrease in proximal fluid reabsorption (delta -2.6 +/- 0.9 nl/min per mm, P < 0.05). When lanthanum was infused interstitially, by means of a chronically implanted matrix, there was significant paracellular lanthanum influx from the interstitium into the lumen (143.9 +/- 18.6 pg/min per mm, n = 4). Subsequent VE significantly increased this interstitium-to-lumen influx to 212.1 +/- 29.2 pg/min per mm as proximal reabsorption was significantly decreased by 58% (delta -2.8 +/- 0.8 nl/min per mm, P < 0.05). Thus, VE affects bidirectional paracellular flux in a manner that would decrease proximal reabsorption; paracellular efflux from the lumen to the interstitium was decreased, whereas paracellular influx from the interstitium to the lumen was increased.

Absorption↗
PubMed1997

Opposite paracrine effects of 5-HT and dopamine on Na(+)-Pi cotransport in opossum kidney cells.

Serotonin (5-HT) was recently reported to inhibit cAMP generation in oppossum (OK) cells. We thus investigated the effects of 5-HT upon the Na(+)-Pi cotransport in cultured OK cells and its interactions with dopamine. Incubation of OK cells with 1 nM-10 microM 5-HT resulted in dose-dependent stimulation of Na(+)-Pi contransport (ED50 approximately equal to 8 nM) and also counteracted inhibition of Na(+)-Pi cotransport elicited by dopamine. Pre-incubation with 5-HT decreased cAMP accumulation elicited by forskolin or dopamine and pre-treatment with pertussis toxin abolished both the inhibitory effect of 5-HT upon cAMP levels and stimulation of Na(+)-Pi cotransport. Incubation of OK cells with the 5-HT precursor 5-hydroxytryptophan resulted in time- and dose-dependent accumulation of 5-HT in the medium that also elicited an increase in Na(+)-Pi cotransport. Both the effects of 5-HT and dopamine on Na(+)-Pi cotransport were prevented by carbidopa. The stimulatory effect of 5-HT was specific for the Na(+)-Pi cotransport system since no effects were observed on Na(+)-alanine cotransport. The results indicate that 5-HT stimulates Na(+)-Pi cotransport at least in part via inhibition of cAMP accumulation. We propose that 5-HT and dopamine have opposite actions as paracrine/autocrine regulators of Na(+)-Pi cotransport via opposite effects upon cAMP formation.

5-Hydroxytryptophan↗
PubMed1996

Propranolol blocks the hypophosphaturia of acute respiratory alkalosis in human subjects.

Respiratory alkalosis (RA) is seen in diverse clinical conditions including tissue hypoxia, malignancy, neurologic disorders, febrile states, pregnancy, and hepatic failure. Acute RA causes hypophosphaturia in rats, and this effect on renal phosphate handling is reversed by beta-adrenoreceptor antagonism. The objective of the present study was to determine the effect of acute RA on phosphate excretion in human patients in the absence and presence of beta-adrenoreceptor antagonism with propranolol. Twelve normal volunteers, 6 women and 6 men, were studied in two phases, once with placebo and once with intravenous infusion of propranolol. In both groups, 30-minute renal clearances were taken during normoventilation (NV) and during acute RA induced by voluntary hyperventilation. Acute RA produced a significant decrease in plasma phosphate (PPi) in the absence (deltaPPi = -0.16 +/- 0.03 mmol/L) and the presence (deltaPPi = -0.16 +/- 0.05 mmol/L) of propranolol. In the placebo group, fractional excretion of phosphate (FEPi) decreased from 24.1% +/- 3.4% in NV to 19.2% +/- 2.6% in RA. This was associated with a significant decrease in parathyroid hormone (PPTH), from 3.38 +/- 0.28 pmol/L in NV to 2.54 +/- 0.30 pmol/L in RA. In the propranolol group, FEPi did not change significantly, from 19.1% +/- 2.7% in NV to 18.7% +/- 3.0% in RA. This also occurred in the face of a decrease in PPTH, from 4.39 +/- 0.53 pmol/L in NV to 2.78 +/- 0.33 pmol/L in RA. Thus propranolol selectively changes the response of FEPi to acute RA while leaving the PPi and PPTH responses unaltered. This suggests that beta-adrenoreceptors play a role in the regulation of the response of renal phosphate handling during acute RA and that this role involves a direct tubular effect on phosphate reabsorption, independent of filtered load and hormonal status. We conclude that beta-adrenoreceptor antagonism blunts the hypophosphaturic effect of acute respiratory alkalosis in human subjects.

Adolescent↗
PubMed1996

Effect of meclofenamate or ketoconazole on the natriuretic response to increased pressure.

Increases in renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion (DRIVE) decrease proximal sodium reabsorption and increase urinary fractional sodium excretion (FENa). This natriuretic response is blunted by inhibition of the cyclooxygenase pathway. However, complicating the interpretation of the effects of cyclooxygenase inhibition on sodium excretion are the following: (1) products of the other pathways of arachidonic acid metabolism, such as the cytochrome P-450 metabolites, may be attenuated when cyclooxygenase activity is reduced; (2) the proximal tubule has a high biosynthetic capacity for cytochrome P-450 metabolites of arachidonic acid. Therefore, the purpose of the present study was to compare blockade of the epoxygenase products of the cytochrome P-450 pathway with ketoconazole to blockade of the cyclooxygenase pathway with meclofenamate on the natriuretic response to increased RIHP during DRIVE. RIHP, fractional excretion of lithium (FELi), FENa and glomerular filtration rate (GFR) were measured before and after DRIVE in control (n = 6), meclofenamate-treated (n = 6), and ketoconazole-treated (n = 5) rats. DRIVE was achieved by infusing 100 microL of 2.5% albumin solution directly into the renal interstitium. In control animals, DRIVE significantly increased RIHP (delta 2.8 +/- 0.6 mm Hg), FELi (delta 13.4% +/- 5.2%), and FENa (delta 1.29% +/- 0.31%). In the ketoconazole-treated group, RIHP (delta 3.9 +/- 0.8 mm Hg), FELi (delta 19.3% +/- 2.0%), and FENa (delta 1.73% +/- 0.43%) also significantly increased. However, the natriuretic response to DRIVE was blunted during cyclooxygenase blockade with meclofenamate when compared with control or ketoconazole-treated animals (FELi (delta 2.5% +/- 1.4%, not significant) and FENa (delta 0.07% +/- 0.18%, not significant), even though the response of RIHP was intact (delta 4.5 +/- 0.4 mm Hg, p < 0.001). These results suggest that the natriuretic response to increased RIHP is dependent on the presence of, but not necessarily the increased synthesis of, products of cyclooxygenase rather than the cytochrome P-450 epoxygenase pathway for arachidonic acid metabolism.

Animals↗
PubMed1996

Phosphaturic effect of L-NMMA in the presence of parathyroid hormone.

The objective of this study was to examine the effect of NG-monomethyl-L-arginine (L-NMMA) on phosphate excretion in the presence and absence of parathyroid hormone (PTH). Renal clearances were obtained before and during infusion of L-NMMA (15 mg/kg bolus and 500 micrograms.kg-1.min-1 infusion) in Sprague-Dawley rats with intact parathyroid glands (n = 6), in thyroparathyroidectomized (TPTX) rats receiving a constant infusion of PTH-(1-34) (0.01-0.03 U.kg-1.min-1) (n = 11) throughout the experiment, or in TPTX rats, that received an acute infusion of PTH-(1-34) (33 U/kg bolus and 1 U.kg-1.min-1 infusion) after L-NMMA infusion alone (n = 7). In rats with intact parathyroid glands, L-NMMA increased the fractional excretions of phosphate (FEPi) and sodium (FENa) and mean arterial pressure (MAP) (delta 8.6 +/- 1.5%, delta 0.62 +/- 0.1%, and delta 26.7 +/- 4.9 mmHg, respectively; P < 0.05). In TPTX rats receiving a constant infusion of PTH, L-NMMA again increased FEPi, FENa, and MAP (delta 9.5 +/- 3.6%, delta 1.1 +/- 0.4%, and delta 28.4 +/- 4.5 mmHg, respectively; P < 0.05). However, in TPTX rats, L-NMMA alone did not increase FEPi (delta 0.9 +/- 0.3%), whereas the subsequent infusion of PTH with L-NMMA increased FEPi (delta 15.6 +/- 3.1%; P < 0.05). In an additional group of intact and TPTX rats, the fractional excretion of lithium (FELi) was measured as an index of proximal reabsorption. L-NMMA increased FELi in intact rats (delta 13.2 +/- 2.6%; P < 0.05), but not in TPTX rats (delta 4.2 +/- 3.3%). In conclusion, L-NMMA increases phosphate excretion in association with increases in MAP and FENa, and this phosphaturic effect is dependent on the presence of PTH.

Animals↗
PubMed1996

Reversal of the antinatriuretic effect of prostaglandin E2 by verapamil in the rat.

Previous studies have demonstrated that prostaglandin E2 (PGE2) infusion increases intrarenal angiotensin-II (ANG-II) formation and decreases sodium excretion in the rat. PGE2 infusion may have direct tubular effects or indirect effects through increased intrarenal ANG-II. In the present study, the calcium channel blocker verapamil was used to determine whether it would reverse the PGE2-induced decrease in sodium excretion. To minimize any systemic and hemodynamic influences, verapamil and PGE2 were infused directly into the renal interstitium via a chronically implanted matrix. Fractional sodium excretion (FENa), glomerular filtration rate (GFR), mean arterial pressure (MAP), and plasma renin activity (PRA) were measured before and during renal interstitial infusion of PGE2 (10(-5) M) and/or verapamil (10(-3) M) in rats pretreated with indomethacin. The renal interstitial infusion of PGE2 alone significantly decreased FENa (delta-1.0 +/- 0.2%), whereas the addition of verapamil reversed the effect of PGE2 and significantly increased FENa (delta 2.6 +/- 0.3%, n = 9). The renal interstitial infusion of verapamil alone markedly increased FENa (delta 1.7 +/- 0.3%, n = 7), and this natriuresis was accompanied by a significant decrease in PRA (delta-0.6 +/- 0.1 ng/ml/h, p < 0.05). The addition of PGE2 to the interstitial infusion did not further affect FENa or PRA. There was a significant difference between the effect of interstitial PGE2 infusion and interstitial PGE2 infusion and interstitial verapamil infusion on PRa (delta 1.9 +/- 0.8 vs. delta -0.6 +/- 0.1 ng/ml/h, p < 0.05). GFR and MAP remained unchanged in response to the renal interstitial infusion of PGE2 and/or verapamil. In conclusion, verapamil reversed the PGE2-induced antinatriuresis in the rat.

Animals↗
PubMed1996

Effect of bromotetramisole on renal phosphate excretion.

Levamisole inhibits alkaline phosphatase (ALP) activity in kidney brush border membranes and increases phosphate excretion in vivo in dogs and rats. I-p-Bromotetramisole (I-BR) is a more potent analog of levamisole in regard to inhibition of ALP activity in vitro, but had no effect on phosphate transport by in vitro proximal tubules of the rabbit. Since its effect on phosphate excretion in vivo has not been studied, the present study tested the effects of infusion of I-BR on phosphate excretion in Sprague-Dawley rats. Fractional excretion of phosphate (FEPi) was measured in thyroparathyroidectomized Sprague-Dawley rats before and during a systemic infusion at 0.8 ml/min of 10 mM I-p-Bromotetramisole oxalate (I-BR, n = 6), or the inactive isomer d-p-Bromotetramisole oxalate (d-BR, n = 5). The FEPi increased significantly from 4.7% +/- 0.9% to 13.4% +/- 3.1% in response to I-BR whereas there were no changes in FEPi with inactive d-BR. In conclusion, systemic infusion of I-p-Bromotetramisole increases FEPi in Sprague-Dawley rats.

Alkaline Phosphatase↗
PubMed1995

Interaction of the renal nerves and prostaglandins on the phosphaturic response to PTH in phosphate-deprived rats.

Previous studies demonstrated that catecholamines modulate the phosphaturic response to parathyroid hormone (PTH) in normal rats. The present study was performed to determine the effect of unilateral renal denervation (DNX) and the interaction with prostaglandin synthesis on the blunted phosphaturic response to PTH in phosphate-deprived rats. One week before the acute experiment, rats were anesthetized, and the left kidney was denervated or sham surgery was performed. Rats were fed either a low-phosphate diet (LPD, 0.07%) or a normal-phosphate diet (NPD, 0.7%) for 2 days before the experiment. All rats were thyroparathyroidectomized (TPTX). Control clearances were taken from the left kidney 2 h after TPTX. PTH (33 U/kg + 1 U.kg-1.min-1) was infused for 45 min, and then the urine collections were repeated. In phosphate-deprived rats with an innervated kidney, PTH infusion resulted in a blunted phosphaturic response [changed fractional excretion of phosphate (delta FEPi) of 9.2 +/- 3.7%, n = 9] compared with rats fed NPD (delta FEPi 45.7 +/- 9.3%, n = 6) or those in the phosphate-deprived group with renal DNX (delta FEPi 23.6 +/- 5.0%, n = 12). Indomethacin pretreatment (3 mg/kg) markedly attenuated the phosphaturic response to PTH in phosphate-deprived rats with a denervated kidney (delta FEPi, 3.2 +/- 1.3%, n = 7) but not in animals fed an LPD with innervated kidneys or in rats fed an NPD. Infusion of Iloprost (2 ng.kg-1.min-1), a stable prostaglandin I2 analogue, in indomethacin-treated phosphate-deprived rats enhanced the phosphaturic response to PTH in rats with a denervated kidney (delta FEPi 17.3 +/- 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Comparison of systemic and direct intrarenal angiotensin II blockade on sodium excretion in rats.

To dissociate the renal effects from the systemic effects of angiotensin II blockade, the present study was designed to determine the effects of systemic and renal interstitial infusion of the specific angiotensin II (ANG II) receptor antagonist, losartan, on blood pressure and sodium excretion in rats fed a low-, normal, or high-sodium diet. Fractional sodium excretion (FENa) and mean arterial pressure (MAP) were measured in rats before and during systemic infusion of losartan (10 mg/kg) or renal interstitial infusion of losartan (3 mg/kg) by means of a chronically implanted matrix. In rats fed a low- or normal sodium diet, systemic infusion of losartan markedly decreased MAP (delta -21 +/- 2, delta -10 +/- 2 mmHg, respectively; P < 0.05) with an accompanying fall in FENa (delta -0.10 +/- 0.05, delta -0.91 +/- 0.40%, respectively; P < 0.05). In contrast, preferential blockade of renal ANG II with renal interstitial losartan infusion resulted in an increase in FENa (delta 0.13 +/- 0.04, delta 0.95 +/- 0.45%, respectively; P < 0.05) and no significant change in MAP. In rats fed a high-sodium diet, both systemic and renal interstitial infusion of losartan increased FENa (delta 1.90 +/- 0.26, delta 1.40 +/- 0.56%, respectively; P < 0.05). Although systemic infusion of losartan decreased MAP (delta -4.4 +/- 0.6 mmHg, P < 0.05) in rats fed a high-sodium diet, the reduction in MAP was much less than that in rats fed a low- and normal sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Role of dopamine in the exaggerated phosphaturic response to parathyroid hormone in the remnant kidney.

The remnant kidney (RK) exhibits an exaggerated phosphaturic response to parathyroid hormone (PTH) infusion. Increased urinary dopamine synthesis per nephron has been demonstrated in the remnant kidney, and dopamine infusion is phosphaturic. Therefore, the role of dopamine in the exaggerated phosphaturic response to PTH infusion in the RK was evaluated. To obtain the RK model, Sprague-Dawley rats were anesthetized and subjected to right nephrectomy as well as surgical ablation of the left renal poles. Sham surgery was performed in the other groups of rats. Four weeks later, acute experiments were performed in these animals. Two hours after thyroparathyroidectomy, a control clearance was taken. Subsequently, PTH (33 U/kg bolus, 1 U/kg/min) was infused for 60 minutes, followed by a 30-minute experimental clearance. In the rats with an RK, the increase in the fractional excretion of phosphate (FEPi) in response to PTH infusion was (delta 38.5% +/- 4.2%, n = 12). In an additional group of rats with an RK, the specific DA-1 receptor antagonist (SCH 23390, 25 micrograms/kg/min) was infused for 30 minutes, a control clearance was taken, and then PTH was infused. Infusion of SCH 23390 significantly blunted the phosphaturic response to PTH (FEPi, delta 24.0% +/- 7.7%, n = 7). In contrast, the phosphaturic response to PTH was similar in the rats that underwent sham surgery in the presence (delta FEPi, 25.4% +/- 1.6%, n = 5) and absence of infusion of SCH 23390 (delta FEPi 24.7 +/- 3.1%, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of acute hypoxia on phosphate excretion in rats.

This study evaluated the effect of acute hypoxia on renal handling of phosphate in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes respiratory alkalosis in spontaneously breathing humans and animals. Respiratory alkalosis has been reported to induce a blunted phosphaturic response to PTH. In this study, to avoid the confounding effect of hypocapnia accompanying the hypoxia on phosphate excretion, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. Rats were divided into two main groups depending on the arterial PO2 levels: a hypoxic group (n = 16) and a normoxic group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats without hypocapnia showed a greater increase in fractional excretion of phosphate (FEPi; 37.7 +/- 2.6%, mean +/- SE) compared with normoxic rats (27.4 +/- 2.5%, P < 0.02). During hypocapnia, there was no difference in FEPi between hypoxic and normoxic groups (21.2 +/- 1.5 and 19.5 +/- 1.2%, respectively), and both groups showed a significantly blunted phosphaturic response to PTH compared with normocapnia (P < 0.05 and P < 0.01, respectively). Urinary adenosine 3',5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion between each group. To test whether the phosphaturic effect of PTH in hypoxia and the blunted phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6), and 3) normoxic and hypocapnic rats (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Acute hypocapnia blunts natriuretic and diuretic effects of atrial natriuretic factor in rats.

Recent studies suggest that the autonomic nervous system, when activated by respiratory alkalosis, may attenuate the renal effects of atrial natriuretic factor (ANF). We evaluated the renal responses to infusion of ANF during acute exposure to hypocapnia in the presence or absence of the renal nerves in anesthetized rats. In this study, renal function during hypocapnia was assessed and was compared with renal function during normocapnia produced by normal ventilation as well as by hyperventilation. Rats were divided into three experimental groups (n = 8): 1) a normally ventilated normocapnic (NV-N) (control) group; 2) a hyperventilated normocapnic (HV-N) group; and 3) a hyperventilated hypocapnic (HV-H) group. The innervated (Inn) right kidney served as a control for the contralateral denervated (DNX) kidney. In Inn and DNX kidneys of HV-H rats, an infusion of ANF (12 micrograms.kg-1.h-1) produced a smaller increase in urine flow rate (delta V: 9.8 +/- 3.9 and 1.3 +/- 4.2 microliters/min) and in fractional Na excretion (delta FENa: 1.35 +/- 0.52 and 0.73 +/- 0.58%) compared with NV-N rats (delta V: 37.6 +/- 4.9 and 59.9 +/- 9.7 microliters/min; delta FENa: 3.24 +/- 0.37 and 3.88 +/- 0.65%). No differences were observed in delta V and delta FENa in Inn kidney between HV-H and HV-N groups; however, the attenuated natriuretic and diuretic responses to ANF in DNX kidney of HV-H rats were also observed in comparison with HV-N rats (delta V: 27.4 +/- 4.3 microliters/min; delta FENa: 2.94 +/- 0.48%). ANF induced natriuresis in DNX kidney to the same degree in NV-N and HV-N rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Phosphaturic effect of parathyroid hormone in the spontaneously hypertensive rat.

The Okamoto spontaneously hypertensive rat (SHR) has been reported to have altered phosphate metabolism. Hypophosphaturia in the presence of increased serum parathyroid hormone (PTH) levels has been reported in the SHR. Therefore it has been postulated that the SHR may be hyporesponsive to the phosphaturic effect of endogenous PTH. In addition, the SHR exhibits enhanced renal sympathetic nerve activity. Recent studies demonstrated that stimulation of the renal adrenoreceptors decreases the phosphaturic response to PTH infusion. Thus a hyporesponsiveness to PTH in the SHR may be due in part to higher renal sympathetic tone. The present study determined the phosphaturic effect of a pharmacological dose of PTH (33 U/kg bolus and 1 U.kg-1.min-1 infusion) in the thyroparathyroidectomized SHR compared with its normotensive control, the Wistar Kyoto (WKY) rat. Three groups of clearance experiments were performed on male 10- to 14-wk-old SHR and WKY rats. In the first group of rats, the fractional excretion of phosphate (FEPi) in response to PTH infusion was 35.4 +/- 4.2% in the SHR (n = 6) and 26.2 +/- 3.0% in the WKY rat (n = 6), NS. In the second group, all animals underwent acute unilateral renal denervation (DNX). The FEPi in response to PTH was 35.3 +/- 1.5% in the innervated (INN) kidney of the SHR (n = 10) compared with 27.9 +/- 2.5% in the INN kidney of the WKY rat (n = 11), and 39.1 +/- 1.9% in the DNX kidney of the SHR compared with 30.5 +/- 2.0% in the DNX kidney of the WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Natriuretic response to renal interstitial hydrostatic pressure during angiotensin II blockade.

Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary sodium excretion (UNaV). Experimentally increasing RIHP by direct renal interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule sodium reabsorption. The purpose of the present study was to investigate whether the renin-angiotensin system modulates the natriuretic response to DRIVE. Unilateral nephrectomy and implantation of two polyethylene matrices were performed 3 wk before the acute experiment. Fractional sodium excretion (FENa), RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE in control rats (n = 9) and in rats receiving the angiotensin II (ANG II) receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was achieved by infusing 100 microliters of 2.5% albumin solution directly into the renal interstitium. GFR remained unchanged by DRIVE in both groups. In control animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/- 0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The natriuretic response to DRIVE was significantly enhanced during ANG II receptor blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs. 0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results suggest that the blockade of angiotensin enhances the natriuretic response to increased RIHP during DRIVE.

Angiotensin II↗
PubMed1994

Perfusion pressure and volume status determine the microvascular response of the rat kidney to NG-monomethyl-L-arginine.

This study investigated the role of volume status and perfusion pressure on the hemodynamic response of cortical and medullary renal capillaries to systemic inhibition of nitric oxide. NG-Monomethyl-L-arginine (L-NMMA) was infused intravenously (15-mg/kg bolus and 500-micrograms.min-1.kg-1 infusion), and blood flow in cortical capillaries (QCC) and in descending (QDVR) and ascending vasa recta (QAVR) was measured by fluorescence videomicroscopy in euvolemic and volume-expanded anesthetized Munich-Wistar rats. L-NMMA in euvolemic rats decreased vasa recta blood flow (delta QDVR, 3.97 +/- 0.80 nL/min [P < .01]; delta QAVR, 1.90 +/- 0.39 nL/min [P < .01]; n = 6) and QCC (delta QCC, 0.57 +/- 0.15 nL/min [P < .01]; n = 7) despite increases in renal perfusion pressure (RPP). Fractional excretion of sodium (FENa) remained unchanged. In volume-expanded rats, L-NMMA decreased vasa recta blood flow when RPP increased (delta QDVR, 1.42 +/- 0.79 nL/min [P = .05]; delta QAVR, 1.95 +/- 0.34 nL/min [P < .001]; n = 9) or was held constant by partial aortic occlusion (delta QDVR, 1.19 +/- 0.45 nL/min [P < .05]; delta QAVR, 1.44 +/- 0.40 nL/min [P < .01]; n = 8). QCC was unchanged by L-NMMA when RPP increased (delta QCC, 0.27 +/- 0.20 nL/min; n = 8) but decreased significantly by 0.61 +/- 0.11 nL/min (P < .01, n = 8) when increases in RPP were prevented. FENa increased when RPP increased (delta FENa, 2.47 +/- 0.51%; P < .001) and was held constant (delta FENa, 2.64 +/- 0.46%; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗