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J L Troy

Publications and source records attributed to J L Troy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of an atrial natriuretic peptide receptor antagonist on glomerular hyperfiltration in diabetic rats.

Previous studies from this laboratory implicated atrial natriuretic peptide (ANP) as a possible mediator of glomerular hyperfiltration in diabetic rats. In this study, the potential of HS-142-1 (HS), a novel polysaccharide compound with ANP receptor antagonist properties, to ameliorate glomerular hyperfiltration in diabetic rats was assessed. Initially, it was confirmed that a bolus iv injection of HS blocked both diuretic and natriuretic responses to exogenous ANP in normal Munich-Wistar rats. The acute effects of HS in moderately hyperglycemic diabetic rats with glomerular hyperfiltration and hyperperfusion were then determined. In diabetic rats, HS (20 mg/kg bolus iv) lowered GFR by approximately 46% from hyperfiltering (1.86 +/- 0.06 mL/min) to normal (1.13 +/- 0.13 mL/min) levels, whereas GFR in vehicle-treated diabetic rats remained unchanged (1.92 +/- 0.08 mL/min to 1.77 +/- 0.09 mL/min). In nondiabetic euvolemic rats, GFR was reduced by 20% after HS, whereas GFR in vehicle-treated controls was unchanged. In contrast, HS had no effect on GFR in hydropenic rats. Effective RPF was not significantly reduced in either diabetic or normal euvolemic rats in response to HS; consequently, significant reductions in filtration fraction were observed in both groups. Urine flow and sodium excretion rates were significantly reduced after HS in both diabetic and nondiabetic groups but not in hydropenic or vehicle-treated groups. These data show that HS ameliorates glomerular hyperfiltration in diabetic rats, further supporting the hypothesis that intrarenal actions of natriuretic peptides contribute significantly to glomerular hyperfiltration in experimental diabetes mellitus.

Animals↗
PubMed1994

HS-142-1, a potent antagonist of natriuretic peptides in vitro and in vivo.

To determine whether HS-142-1 (HS), a potent atrial natriuretic peptide (ANP) receptor antagonist, also inhibits the effects of brain natriuretic peptide (BNP), urodilatin (URO), and C-type natriuretic peptide, in vitro studies were carried out, demonstrating that HS inhibited production of cGMP by rat fetal lung fibroblast cells induced by ANP, BNP, URO, and C-type natriuretic peptide. Acute clearance studies were conducted in euvolemic Munich-Wistar rats under inactin anesthesia to characterize the effects of HS in vivo. In response to ANP, BNP, or URO (4 micrograms/kg priming dose plus 0.5 micrograms/kg per minute for 20 min), urine flow, absolute sodium excretion rates, and fractional sodium excretion exhibited similar increases (four- to fivefold) in vehicle-treated rats; these responses were, however, completely abolished by prior HS treatment. The tendency for GFR to rise during the infusion of natriuretic peptides (NP) was also blocked after HS. By contrast, HS did not block the renal effects of L-arginine, a precursor of nitric oxide, or of furosemide. Furthermore, the inhibition of endogenous NP by HS was associated with small but significant reductions in GFR and absolute and fractional sodium excretion in normal rats under euvolemic but not hydropenic conditions. These studies provide evidence that the observed effects of HS in vivo and in vitro are mediated exclusively by receptors of NP. Together, these data support the view that HS is a highly specific ligand for NP receptors, capable of antagonizing the renal effects not only of exogenous ANP, but also those of BNP and URO.

Animals↗
PubMed1994

TCV 116 prevents progressive renal injury in rats with extensive renal mass ablation.

OBJECTIVE: The objective of this study was to determine the renal protective effects of TCV 116, a novel, non-competitive, angiotensin II type 1 (AT1) receptor antagonist, in rats with 5/6 renal mass ablation. DESIGN: Adult male Wistar rats were subjected to 5/6 nephrectomy and treated continuously with either TCV 116 (group I, n = 8; group III, n = 9) or vehicle (group II, n = 8; group IV, n = 8). The development of elevated systolic blood pressure, 24-h urinary protein excretion, glomerular hemodynamics and glomerular morphology were compared among groups. RESULTS: Systolic blood pressure rapidly reached hypertensive levels in group II, increasing from 175 +/- 8 mmHg after 3 weeks to 221 +/- 15 mmHg after 12 weeks, whereas group I rats remained normotensive (101 +/- 8 to 112 +/- 6 mmHg). Similarly, urinary protein excretion increased from 45 +/- 11 to 104 +/- 18 mg/day in group II, but remained low (6.9 +/- 1 to 19 +/- 4 mg/day) in group I. After 12 weeks, there was an average of 42 +/- 6% glomerulosclerosis in group II, but only 1.6 +/- 0.5% in group I. After 4-6 weeks, a markedly elevated glomerular capillary pressure (62 +/- 1.2 mmHg) was observed in group IV, but the pressure was normal in group III (50 +/- 1.1 mmHg). CONCLUSIONS: These data show that TCV 116 prevents the development of systemic hypertension, glomerular capillary hypertension, proteinuria and glomerulosclerosis in rats with reduced renal mass. We therefore conclude that the renal protection associated with angiotensin I converting enzyme inhibitors and other pharmacologic blockers of the renin-angiotensin system arises chiefly from blockade of AT1 receptor-mediated hemodynamic effects.

Angiotensin Receptor Antagonists↗
PubMed1993

Self assessment.

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Acquired Immunodeficiency Syndrome↗
PubMed1993

A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen, BP180.

Subepidermal blistering associated with the human skin diseases bullous pemphigoid and herpes gestationis has been thought to be an IgG autoantibody-mediated process; however, previous attempts to demonstrate the pathogenicity of patient autoantibodies have been unsuccessful. An immunodominant and potentially pathogenic epitope associated with these blistering diseases has recently been mapped to the extracellular domain of a human epidermal antigen, BP180. Patient autoantibodies that react with this well-defined antigenic site failed to crossreact with the murine form of this autoantigen and thus could not be assayed for pathogenicity in a conventional passive transfer mouse model. As an alternative, rabbit polyclonal antibodies were generated against a segment of the murine BP180 protein homologous with the human BP180 autoantibody-reactive site and were passively transferred into neonatal BALB/c mice. The injected animals developed a subepidermal blistering disease that closely mimicked bullous pemphigoid and herpes gestationis at the clinical, histological, and immunological levels. Autoantibodies that recognize the human BP180 ectodomain are therefore likely to play an initiatory role in the pathogenesis of bullous pemphigoid and herpes gestationis.

Amino Acid Sequence↗
PubMed1993

Pathogenesis of glomerular injury in the fawn-hooded rat: early glomerular capillary hypertension predicts glomerular sclerosis.

Fawn-hooded rats spontaneously develop focal and segmental glomerular sclerosis, systemic hypertension, and proteinuria at a young age. Micropuncture and morphological studies were performed in two inbred strains of fawn-hooded rats, FHH and FHL, with different susceptibilities to develop chronic renal failure. FHH rats have higher values for systolic blood pressure and proteinuria and more rapid development of focal and segmental glomerular sclerosis and subsequent chronic renal failure as compared with genetically closely related FHL rats. FHH and FHL strains and a Wistar control strain, WAG, were matched for age and were studied at 16 wk. FHH, FHL, and WAG-old (WAG-O) strains were matched for weight, and the last group was studied at 22 wk. WAG were also matched for weight to a young group of FHH rats (FHH-Y), and these were studied at 8 wk. In comparison with WAG and WAG-O rats, FHH and FHH-Y rats exhibited an increased in mean glomerular capillary hydraulic pressure (WAG, 52 +/- 1 mm Hg; WAG-O, 47 +/- 2 mm Hg; FHH, 60 +/- 2 mm Hg; FHH-Y, 65 +/- 1 mm Hg), whereas values in FHL animals were intermediate (56 +/- 2 mm Hg). No significant differences in glomerular volume were found among groups. Moderate focal and segmental glomerular sclerosis developed in FHH and FHH-Y rats, with values for older FHH rats being significantly greater than those for WAG, WAG-O, and FHL animals. Thus, the genetically determined sensitivity to develop proteinuria, focal and segmental glomerular sclerosis, and chronic renal failure in fawn-hooded rats correlated with early evidence of glomerular capillary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Determination of glomerular size-selectivity in the normal rat with Ficoll.

Diffusion studies in vitro indicate that Ficoll behaves more like an ideal spherical molecule than does dextran, suggesting that Ficoll would be a better probe of glomerular pore size than the commonly used dextran. To examine the differences between these macromolecules in vivo, the fractional clearances of tritiated Ficoll and dextran were measured over a wide range of molecular sizes (Stokes-Einstein radius, rs, from 19 to 65 A) in normal euvolemic Munich-Wistar rats. Whole-kidney and single-nephron hemodynamic conditions were characterized through a combination of clearance and micropuncture measurements. The fractional clearance, or sieving coefficient (theta), for dextran significantly exceeded that of Ficoll at all molecular sizes examined, theta for dextran being approximately 10 times that for Ficoll for rs greater than 30 A. Thus, the results with Ficoll imply a more size-restrictive barrier than do the results with dextran. The values of theta for Ficoll approximated previously reported values for uncharged globular proteins. Although theta for Ficoll at rs = 35 A was much smaller than the corresponding value for dextran, it was still approximately 30 times greater than typical values of the filtrate-to-plasma concentration ratio reported for serum albumin (a polyanion) in the rat, in agreement with the concept that glomerular charge-selectivity normally plays an important role in the prevention of albuminuria. Three membrane-pore models were compared in their ability to represent the dextran and Ficoll sieving data. A lognormal pore-size distribution in parallel with a nonselective "shunt" pathway was found to be more effective than either an isoporous membrane with a shunt or a purely lognormal distribution. On the basis of these laboratory results and computations, Ficoll may be preferred over dextran in future studies of glomerular size-selectivity.

Animals↗
PubMed1991

Anemia ameliorates progressive renal injury in experimental DOCA-salt hypertension.

To explore the role of systemic hematocrit in the vascular adaptations which characterize desoxycorticosterone-salt hypertension, studies were performed in three groups of rats with uninephrectomy, desoxycorticosterone administration, and 1% saline in the drinking water. One group received recombinant human erythropoietin to increase hematocrit, and another group was subjected to phlebotomy and fed a low-iron diet to induce anemia. Control rats exhibited systemic and glomerular capillary hypertension, proteinuria, and substantial glomerular sclerosis at 8 wk. Erythropoietin modestly increased hematocrit and blood pressure and substantially aggravated glomerular capillary pressure, proteinuria, and glomerular sclerosis. In contrast, reduction of hematocrit with a low-iron diet significantly attenuated systemic and glomerular hypertension, proteinuria, and sclerosis. It was concluded that the pace of progression of glomerular injury can be limited by chronic reduction in hematocrit, which effectively ameliorates both systemic and glomerular hypertension in this model of salt-sensitive hypertensive renal disease.

Anemia↗
PubMed1991

Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

Reversible hexadimethrine-induced alterations in glomerular structure and permeability.

Female Munich-Wistar rats received hexadimethrine (HDM) i.v. until the onset of proteinuria (PEAK)--a period of not more than 30 min. There were four experimental groups: C (control), H (HDM only), HH (HDM and heparin), and HHD (identical to HH but with dextran clearances measured). Rats in groups HH and HHD received a heparin bolus after the PEAK period, whereas rats in group H did not. HDM led to dramatic increases in both albumin and IgG excretion. Glomerular filtration rate and renal plasma flow rate were reduced by 30 to 50% after HDM infusion. Neutral dextran clearances for radii greater than 30 A were elevated during the PEAK period, and, concurrently, there was extensive intraglomerular microthrombosis, obliteration of foot processes, and disruption of filtration slit diaphragms. One hour later, glomerular filtration rate, renal plasma flow rate, dextran clearances, and proteinuria returned to baseline in groups HH and HHD but not in group H. Recovery in heparin-treated rats was associated with reversal of HDM-associated morphological alterations. Membrane pore-size parameters calculated from the dextran clearances indicate that HDM leads to a detect in glomerular size-selectivity. The facts that maximal albuminuria tended to precede maximal excretion of IgG and that increases in albumin excretion were proportionately greater than those of dextran or IgG suggest that HDM also leads to a time-dependent defect in glomerular charge-selectivity.

Albuminuria↗
PubMed1991

Endothelium-derived relaxing factor and the vascular reply to systemic hypertension.

Endogenous nitric oxide is an important modulator of vascular smooth muscle tone. The role of nitric oxide in the vascular adaptation to systemic hypertension was examined by using N omega-monomethyl-L-arginine (L-NMMA; 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused i.v. into several rat models of acute and chronic systemic hypertension. The response to L-NMMA was compared either in uninephrectomized Sprague-Dawley rats treated with deoxycorticosterone on either a high- or low-sodium diet or in untreated uninephrectomized rats on normal chow. Hypertensive deoxycorticosterone rats had a significantly greater pressor response to L-NMMA (139 +/- 2 to 169 +/- 3 mm Hg; N = 9) than did normotensive uninephrectomized rats (112 +/- 4 to 129 +/- 3 mm Hg; N = 7) or deoxycortisterone treated rats on a low-sodium diet (108 +/- 2 to 121 +/- 3 mm Hg; N = 9). By contrast, hypertension induced by the vasoconstrictor angiotensin II did not have an enhanced response (134 +/- 3 to 154 +/- 4 mm Hg; N = 7) nor did spontaneously hypertensive rats (164 +/- 4 to 175 +/- 4 mm Hg; N = 6). This dose of L-NMMA had minimal effects on renal hemodynamics in the normotensive and hypertensive animals, except for those receiving angiotensin II where it led to substantial reductions of inulin and para-aminohippurate clearance. In conclusion, these data point to a role for nitric oxide in the vascular adaptation to volume-mediated hypertension, an effect that was not observed in vasoconstrictor-induced hypertension.

Acute Disease↗
PubMed1990

Self-healing dystrophic calcinosis following trauma with transepidermal elimination.

An unusual case of dystrophic calcinosis that occurred following trauma is presented. Calcinosis cutis is the deposition of calcium phosphate into the skin. It is classified as dystrophic if calcium and phosphorous levels are normal and tissue damage is present, idiopathic if calcium and phosphorous levels are normal and no tissue damage is present, or metastatic if there is hypercalcemia or hyperphosphatemia. The numerous causes of underlying tissue damage associated with dystrophic calcinosis are discussed.

Adolescent↗
PubMed1988

Atrial natriuretic peptide and furosemide effects on hydraulic pressure in the renal papilla.

Atrial peptides (ANP) have been shown to preferentially increase blood flow to juxtamedullary nephrons and to augment vasa recta blood flow. To determine the effect of this alteration in intrarenal blood flow distribution on pressure relationships in inner medullary structures and their significance as a determinant of ANP-induced natriuresis, we measured hydraulic pressures in vascular and tubule elements of the renal papilla exposed in Munich-Wistar rats in vivo during an euvolemic baseline period and again during an experimental period. Rats in Group 1 received intravenous infusion of rANP administered as a 4 micrograms/kg prime and 0.5 microgram/kg/min continuous infusion, and were maintained euvolemic by plasma replacement. Infusion of ANP resulted in significant natriuresis, diuresis and increase in inulin clearance. Within 90 seconds of initiation of this systemic infusion, vasa recta hydraulic pressures were markedly increased and exceeded the small pressure increment occurring in loops of Henle and collecting ducts. Infusion of furosemide in Group 2 rats at a dosage which reproduced the increase in urine flow in Group 1 was associated with small and equivalent increases in both vascular and tubule elements, indicating that the differential pressure response observed in Group 1 was not due to increased tubule fluid flow rates, but was rather a specific ANP-induced vascular effect. Group 3 rats received an infusion of ANP in a setting where its whole kidney hemodynamic effects were prevented. This resulted in a marked blunting of natriuresis and diuresis, and obliteration of the pressure differential between vasa recta and tubules observed in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of intermittent feeding on renal hemodynamics in conscious rats.

The hemodynamic influences of many forms of dietary restriction have not been studied in the conscious rat. To examine the effect of one regimen of dietary restriction, alternate-day feeding, on renal hemodynamics, we performed 56 clearance studies in 20 unanesthetized, previously catheterized male Sprague-Dawley rats at mean age 30 wk. Group 1 rats (n = 10) were given standard chow only on alternate days for 25 wk and then studied after feeding and after fasting days, whereas group 2 rats (n = 10) were fed ad libitum during the same period and then studied randomly. In group 1, glomerular filtration rate (GFR, clearance of inulin) and renal blood flow [RBF, clearance of PAH/(1 - hematocrit)] increased 23 and 19%, respectively, after feeding days compared with fasting days (GFR, 4.25 vs. 3.47 ml/min, P less than 0.005; RBF, 22.2 vs. 18.6 ml/min, P less than 0.025). After feeding, mean arterial pressure and plasma protein concentration were unchanged, hematocrit increased slightly, and fractional excretion of sodium rose from 0.23 to 0.57%. Both GFR and RBF averaged 31% less in group 1 than in group 2 but, when factored by body weight, the differences were abolished. The results indicate that alternate-day feeding causes substantial oscillations in GFR and RBF in healthy awake rats through mechanisms unlikely to involve changes in extracellular fluid volume alone and limits GFR and RBF to average values markedly lower than those observed for larger ad libitum-fed rats of the same age.

Animals↗