Effect of atrial natriuretic factor on brush border membrane transport of phosphate in phosphate-deprived rats.
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Animals↗
Biomedical subjects
T G Hammond
Publications and source records attributed to T G Hammond.
Control of biliary phospholipid secretion. Effect of continuous and discontinuous infusion of taurocholate on biliary phospholipid secretion.
A major determinant of biliary lipid secretion is bile-salt secretion. Taurocholate (TC), a micelle-forming bile salt, was infused continuously at different rates in both isolated perfused livers and biliary-fistula rats. In both of these systems, infusion of TC brought about an elevated secretion of phosphatidylcholine for the duration of the TC infusion period. Initial phospholipid/bile-salt ratios in the bile were higher in the whole-animal model than in isolated livers, but at the higher infusion rates both secreted approx. 6 mol of phospholipid for every 100 mol of bile salt. The secretion of phospholipid, which was maintained even at high rates of bile-salt infusion, suggest a continuous and regulated phospholipid supply and secretion mechanism. In contrast, however, multiple short pulses of TC to the perfused liver, which brought about relatively equal biliary bile-salt output pulses, did not bring about equal phospholipid outputs, since the phospholipid peak size declined with each bile-salt pulse. These experiments taken together suggest either that a threshold (intracellular) bile-salt concentration may be required to 'switch-on' the phospholipid supply and that it may need to be maintained for continuous biliary phospholipid supply to the canalicular membrane.
Animals↗
Effect of exogenous angiotensin II infusion after one year of captopril therapy in essential hypertension.
The effect of exogenous angiotensin II on plasma renin activity (PRA), plasma renin concentration (PRC) and plasma aldosterone (PA) was investigated in a group of 8 patients with essential hypertension after one year of captopril therapy. The results were compared with those obtained in a group of 18 normotensive volunteers not on captopril. Angiotensin II was infused at increasing doses until a pressor response (increase of diastolic blood pressure by 20 mm Hg) was evoked. The normotensive volunteers exhibited the expected decline of PRA during angiotensin II infusion. However, no significant change was observed in PRA nor in PRC levels in the group of hypertensive patients. The PA values increased significantly both in volunteers and patients (P less than 0.02). The dose of angiotensin II necessary to evoke a pressor response was higher in the hypertensive patients than in the normotensive volunteers (6.0 +/- 2.6 s.d. ng/kg/min vs 2.5 +/- 0.9; P less than 0.01). We conclude that patients with essential hypertension, after chronic treatment with captopril, show no inhibition of renin secretion in contrast with the controls. They also require more angiotensin II to evoke a pressor response during infusion of this peptide.
Adult↗
Synthetic atrial natriuretic factor decreases renal tubular phosphate reabsorption in rats.
Atrial natriuretic factor (ANF), a family of peptides isolated from cardiac atria, has marked effects on sodium excretion. A synthetic 26 amino acid sequence of ANF peptide has also been shown to be phosphaturic. However, it is difficult to assess whether the phosphaturia is due to changes in tubular reabsorption of phosphate without control of filtered load of phosphate. In the present study, the hypothesis that ANF peptide decreases tubular phosphate reabsorption was tested by using graded phosphate infusions of 0, 1, 2, and 3 mumol/min in thyroparathyroidectomized rats. Further, reabsorbed phosphate was similarly assessed in rats infused with parathyroid hormone (PTH) to allow comparison with a known phosphaturic hormone. ANF peptide decreased reabsorbed phosphate compared with saline controls (2.72 +/- 0.28 mumol/ml GFR compared with 3.35 +/- 0.35, P less than 0.05) but not as much as a maximally phosphaturic dose of PTH (2.04 +/- 0.13 mumol/ml GFR). We conclude that synthetic ANF peptide decreases tubular phosphate reabsorption in vivo.
Absorption↗
Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules.
The newly discovered peptides extracted from cardiac atria, atrial natriuretic factors (ANFs), when administered parenterally cause renal hemodynamic changes and natriuresis. The nephron sites and cellular mechanism accounting for profound increase in Na+ excretion in response to ANFs are not yet clarified. In the present study we investigated whether synthetic ANF peptide alters the reabsorption of Na+ and reabsorption of solutes cotransported with Na+ in the proximal tubules of rats. Synthetic ANF peptide consisting of 26 amino acids, 4 micrograms/kg body wt/h, or vehicle in controls, was infused to surgically thyroparathyroidectomized anesthetized rats. After determination of the fractional excretion (FE) of electrolytes (Na+, K+, Pi, Ca2+, Mg2+, HCO3), the kidneys were removed and luminal brush border membrane vesicles (BBMVs) were prepared from renal cortex. Solute transport was measured in BBMVs by rapid filtration techniques. Infusion of ANF peptide increased FENa, FEPi, and FEHCO3; but FECa, FEK, and FEMg were not changed. The increase in FENa was significantly correlated, on the one hand, with increase of FEPi (r = 0.9, n = 7; P less than 0.01) and with increase of FEHCO3 (r = 0.89, n = 7; P less than 0.01). On the other hand, FENa did not correlate with FEK, FECa, or with FEMg. The Na+ gradient-dependent uptake of Pi by BBMVs prepared from renal cortex of rats receiving ANF infusion was significantly (P less than 0.05) decreased (-25%), whereas the Na+ gradient-dependent uptake of L-[3H]proline and of D-[3H]glucose or the diffusional uptake of 22Na+ were not changed. ANF-elicited change in FEPi showed a close inverse correlation with decrease of Na+-dependent Pi uptake by BBMVs isolated from infused rats (r = 0.99, n = 7; P less than 0.001). Direct addition of ANF to BBMVs in vitro did not change the Na+ gradient-dependent Pi uptake. In rats infused with ANF, the rate of amiloride-sensitive Na+-H+ exchange across the brush border membrane (BBM) was significantly (P less than 0.05) decreased (-40%), whereas the diffusional 22Na+ uptake (0.5 min) and the equilibrium (120 min) uptake of 22Na+ were not changed. The inhibition of Na+-H+ exchange after ANF was likely due to alteration of the BBM antiporter itself, in that the H+ conductance of BBMVs was not increased. We conclude that synthetic ANF (a) decreases tubular Na+ reabsorption linked to reabsorption of HCO3 in proximal tubules, and (b) inhibits proximal tubular reabsorption of Pi coupled to Na+ reabsorption, independent of secretion and/or action of parathyroid hormone or calcitonin. These ANF effects are associated with inhibition of Na+-Pi synport and of Na+-H+ antiport in luminal BBMs. Our findings document that inhibition of Na+-coupled transport processes in proximal tubules is an integral part of the renal response to ANF.
Animals↗
Lung oedema--microscopic detection.
During routine inhalation toxicity studies, microscopic examination of tissues from lungs which have shown small, but statistically significant increases, in organ weight has failed to show evidence of any pathological change. Historically, increases, thought to be due to mild oedema, have been difficult to identify microscopically. A method suitable for dealing with large numbers of rodents has been developed, which can detect microscopically changes associated with small increases in lung weight. The lungs were inflated with formalin vapour and fixed in 10% buffered formalin. Histological processing methods were varied to obtain the best demonstration of oedema. Fixation methods were compared using alpha-naphthylthiourea-induced oedematous lungs. The left lobe was inflated with formalin vapour and the rest of the lung was distended with 10% buffered formalin. The best demonstration of oedema followed formalin vapour fixation. Evidence of oedema, indicated by lung weight increases of approximately 10%, was seen microscopically in formalin-vapour-fixed lungs, but was not seen in the lobes distended with 10% buffered formalin. Application of this technique to other species including cats and dogs has also proved successful.
Animals↗
Renin-angiotensin-aldosterone system in nephrotic syndrome.
Previous studies on the renin-angiotensin-aldosterone system and fluid volumes in patients with nephrotic syndrome have not considered the nature of the underlying renal lesion. We compared plasma renin concentration (PRC), plasma aldosterone (PA), and plasma volume in three groups of patients: five nephrotic patients with minimal change disease on renal biopsy, seven nephrotic patients with other renal histopathology, and a control group of eight patients investigated for glomerulonephritis with no past or present nephrosis. PRC and PA were significantly greater in nephrotic patients with minimal change disease than other renal histopathology (Supine PRC 42 +/- 7 microIU/mL compared with 14 +/- 4, P less than 0.01; ambulant PRC 56 +/- 7 microIU/mL compared with 29 +/- 10, P less than 0.05; supine PA 158 +/- 55 pg/mL compared with 53 +/- 13, P less than 0.05; and ambulant PA 167 +/- 57 pg/mL compared with 29 +/- 10, P less than 0.05. Plasma volume was similar in all three groups, contrary to predictions from the Starling capillary fluid exchange hypothesis. Nephrosis may be characterized by different pathophysiologic groups according to the underlying renal histopathology. High plasma renin and aldosterone levels may be markers for minimal change disease.
Adolescent↗
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↗
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↗
Primary hyperaldosteronism in pregnancy.
We report a case of primary hyperaldosteronism in a 37-year-old woman presenting early in pregnancy with hypertension and hypokalaemia. Plasma renin concentration was suppressed and unaffected by sodium restriction or upright posture at 16 and 35 weeks gestation, or seven days post-partum. Recumbent plasma aldosterone was elevated, and normal postural response lost both at 35 weeks gestation and seven days post-partum. Vaginal delivery, following induction at 38 weeks, was uncomplicated. Two months postpartum C.T. scan and adrenal venous catheterisation studies indicated a left sided adenoma and left adrenalectomy was performed. Within seven days the patient was normotensive with normal serum potassium and urinary aldosterone on no treatment.
Adenoma↗
Differential effects of two NMDA receptor antagonists on cognitive--behavioral performance in young nonhuman primates II.
The present experiment examined the effects of chronic exposure to remacemide (an NMDA antagonist that also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors more selectively) on the acquisition of color and position discrimination and short-term memory behavior in juvenile rhesus monkeys. Throughout the 2-year dosing period, a conditioned position responding (CPR) task was used to assess color and position discrimination and a delayed matching-to-sample (DMTS) task was used to assess memory. Chronic exposure to high doses of either drug delayed the acquisition of accurate color and position discrimination without altering response rates. In the case of MK-801, these effects abated within 6 months of the start of treatment. In the case of remacemide, the effects persisted for 17 months of dosing. Neither compound significantly altered performance of the short-term memory task at any time point or at any dose tested. The fact that the effects of remacemide on behavioral performance were more persistent than those seen for MK-801 suggests that tolerance may develop to the behavioral effects of MK-801, which does not develop to the effects of remacemide. Alternatively, these results may suggest that the concurrent antagonism of NMDA receptors and fast sodium channels may have more profound consequences for behavior than does the antagonism of NMDA receptors alone.
Acetamides↗
Differential effects of two NMDA receptor antagonists on cognitive-behavioral development in nonhuman primates I.
The present experiment examined effects of chronic exposure to remacemide (an N-methyl-D-aspartate [NMDA] antagonist which also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors, exclusively) on learning and motivation in young rhesus monkeys. Remacemide (20 or 50 mg/kg/day) or MK-801 (0.1 or 1.0 mg/kg/day) was administered every day to separate groups of animals via orogastric gavage for up to 2 years. Immediately prior to dosing, 5 days per week (M--F), throughout the 2-year dosing period, an incremental repeated acquisition (IRA) task was used to assess learning and a progressive ratio (PR) task was used to assess motivation. The results indicate an effect of 50 mg/kg/day remacemide to impair learning (IRA) which persisted even after drug treatment was discontinued. MK-801 had no effect on learning but transiently increased motivation. Because the effects of remacemide occurred independently of changes in motivation or response rates, they are likely due to specific cognitive impairments and are not due to an inability of subjects to fulfill the motoric requirements of the task. The fact that MK-801 did not alter learning suggests that NMDA antagonism alone may be insufficient to produce learning deficits in young monkeys and that such deficits may rely on the ancillary blockade of fast sodium channels.
Acetamides↗
Assessing the potential toxicity of MK-801 and remacemide: chronic exposure in juvenile rhesus monkeys.
The present experiment examined the effects of chronic exposure to either 0.1 or 1.0 mg/kg MK-801 [a selective N-methyl-D-aspartate (NMDA) receptor antagonist] or 20.0 or 50.0 mg/kg remacemide (an NMDA receptor antagonist which also blocks fast sodium channels) in juvenile rhesus monkeys. Endpoints were monitored to provide a general index of subjects' health and included measures of clinical chemistry, hematology, ophthalmology, spontaneous home-cage behavior, and peak drug plasma levels. In general, both drugs were well tolerated and produced no treatment-related effects during 2 years of dosing and assessment. Periodic plasma drug level determinations provided limited evidence that both compounds may induce their own metabolism. The present results contrast sharply with previously reported effects of long-lasting impairments in the acquisition of incremental learning and in the development of color and position discrimination in these same subjects. These observations highlight the importance of collecting a broad range of toxicology data, including tests of cognitive function, to make comprehensive assessments of new drug safety. In the present case, the less obvious effects of these drugs on cognition defined the toxicologic response.
Acetamides↗
Pneumoperitoneum in peritoneal dialysis patients: significance of diagnosis by CT.
OBJECTIVE: Pneumoperitoneum diagnosed by plain radiography is often a sign of gastrointestinal perforation and is unusual (0.17%) in patients on continuous ambulatory peritoneal dialysis (CAPD). These patients are prone to bacterial peritonitis, which can have overlapping clinical findings with perforated viscus. Because CT is often used to screen symptomatic CAPD patients, the reliability of pneumoperitoneum as a diagnostic sign is examined. MATERIALS AND METHODS: Records of 433 CAPD patients were examined; of these, 56 patients had had CT while on CAPD (rupture, 6; nonrupture, 50). Plain radiography and CT were examined for free air and fluid. Patients were classified according to the amount of free air detected. RESULTS: Patients with ruptured viscus had pneumoperitoneum in 5 of 6 cases by CT and 4 of 6 by plain radiography. Excluding free air, ruptured viscus could only be diagnosed in 1 of the 6 patients by CT. Patients without rupture had pneumoperitoneum in 15 of 50 cases by CT and 2 of 46 by plain radiography. No instance of pneumoperitoneum was discovered on plain radiography and not CT. CONCLUSION: Pneumoperitoneum was found by CT in 30% of nonrupture CAPD patients, therefore, CT appeared to be more sensitive than plain radiography for its detection. The presence, quantity, and distribution of free air are not helpful in separating perforations from nonperforations. The lack of pneumoperitoneum on CT was found to be a useful but not absolute diagnostic sign to exclude gastrointestinal rupture.
Aged↗
Renal autotransplants in sheep: investigation of renal function and renovascular hypertension.
1. A novel surgical preparation of sheep with a cervical renal autotransplant has been developed. 2. Glomerular filtration rate and effective renal plasma flow were 25.1 +/- 1.0 ml/min and 208 +/- 10 ml/min respectively (n = 26). 3. The responses to water load and deprivation, to AVP injection, to Na depletion and intravenous hypertonic saline load show the kidneys responded in an appropriate physiological manner. 4. Constriction of the carotid-renal artery to reduce mean renal arterial pressure to 23 +/- 4 mmHg (n = 4) resulted in an increase in systemic mean arterial pressure from 70 +/- 4 mmHg to 75 +/- 4 mmHg within 5 min. Systemic blood pressure further increased to 110 +/- 7 mmHg with 2 h of constriction, when renal arterial pressure had increased to 45 +/- 2 mmHg.
Animals↗
Effects of converting enzyme inhibition with captopril on renal function in normal and ACTH treated sheep.
1. The effect on renal function in sheep of inhibiting converting enzyme with captopril was examined before and after 5 days ACTH administration. 2. Glomerular filtration rate, effective renal plasma flow, effective renal blood flow, mean arterial pressure and plasma sodium were all significantly increased by ACTH treatment and plasma potassium was decreased. Captopril (20 mg i.v.) had no effect on renal function or blood pressure before or after ACTH treatment, although urinary potassium excretion decreased following captopril on day 6 of ACTH treatment. 3. The increase in glomerular filtration rate and effective renal plasma flow seen with ACTH treatment in sheep does not appear to be mediated by the reninangiotensin system.
Adrenocorticotropic Hormone↗
[Vesicular flow in epithelial cells: physiopathologic importance of two multiligand receptors].
Epithelial structures lining the proximal tubule and the yolk sac are characterized by a high rate of internalization followed by degradation of the proteins exposed to their apical pole. This function implies the expression by these epithelia of specialized proteins which have the ability to bind numerous ligands and/or lysosomal targeting properties. An improved knowledge of these molecules is needed since their expression in a limited number of epithelia may account for the specificity of some pathologies induced in particular by toxins. This paper deals with two such "candidate" proteins, gp330/megalin and gp280 which have been expressed in all species studied. gp280 is the target of teratogenic antibodies and is identified here as the receptor for intrinsic factor-cobalamin complexes but in all likelihood also binds other ligands. Antibodies to gp280 markedly stimulate the fusion of renal endosomes suggesting that it may play a role in targeting processes. gp330/megalin has been recently identified as the ligand of polybasic compounds such as gentamicin and is a key component in the internalization of the drug by tubular cells leading to renal toxicity. gp330/megalin also intervenes in endosomal fusion and some of its toxic properties may be mediated by this route.
Animals↗