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L C Moore

Publications and source records attributed to L C Moore.

At least 19 recordsLinked to original sources
PubMed1996

Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue.

Peripheral nerve injury may lead to a chronic neuropathic pain state that results from an increase in excitability of central neurons. This central sensitization is mediated via an N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). As NO is suggested to play a role in nociceptive transmission following nerve injury, we examined for altered NO synthase activity at multiple levels of peripheral and spinal neural tissue in a rat model of neuropathic pain. Peripheral neuropathy was induced in rats (N = 12) by ligation of the left L5 and L6 nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical stimuli confirmed the presence of a neuropathic pain state. Samples of the lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nerves were obtained from the lesioned and contralateral sides at 2 and 4 weeks after neuropathic surgery (N = 6 per group). In the lumbar spinal cord, a bilateral decrease in nitric oxide synthase (NOS) activity was observed 2 and 4 weeks after neuropathic surgery. NOS activity was increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activity in the DRG may be an early mechanism for inducing more central changes. The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from increased NO production in the spinal dorsal root ganglia. Multiple alterations in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting from peripheral nerve injury. (Preliminary results of these studies have been presented in abstract form at the annual meetings of the Society for Neuroscience, 1994, and the American Society of Anesthesiologists, 1994).

Analysis of Variance↗
PubMed1996

Capillary electrophoresis for the determination of glomerular filtration rate using nonradioactive iohexol.

High-performance liquid chromatography (HPLC) has been used as an alternative to the isotopic method to calculate glomerular filtration rate (GFR). With the HPLC method, serum iohexol or iothalamate levels are measured, and the plasma clearance rate of the compound is used as a surrogate for GFR. However, HPLC is a labor-intensive procedure, which limits its usefulness in the clinical setting. Capillary electrophoresis, a newer technique in which electrophoretic separations are performed in capillary tubes, is easier and faster than HPLC. We used capillary electrophoresis for the determination of serum iohexol levels and the calculation of GFR. Patients underwent a simultaneous 125I-iothalamate clearance test and a plasma iohexol clearance test to determine GFR. Mean GFR (+/-SD) was 70.9 +/- 29.9 mL/min (range, 14.5 to 131 mL/min) in 52 patients as determined by standard iothalamate clearance methods. For iohexol clearance, the correlation coefficient and standard error were 0.93 and 10.9 mL/min, respectively, using capillary electrophoresis compared with the iothalamate method. Capillary electrophoresis is a simple, rapid method that can be used to calculate GFR and provides results at least as accurate as those obtained by HPLC and x-ray fluorescence.

Adult↗
PubMed1996

Measurement of glomerular filtration rate using nonradioactive Iohexol: comparison of two one-compartment models.

Radioisotopic methods for the determination of the glomerular filtration rate (GFR) are highly accurate but require the collection of multiple blood and urine samples and are costly to perform due to personnel, material, and analysis costs. Nonradioactive methods of GFR determination have the potential of minimizing procedure costs while preserving accuracy. We determined the GFR simultaneously by 125I-iothalamate and nonradioactive iohexol clearance methods in 41 adults. The study group consisted of 54% males, with a mean age of 50.7 (range 28-79) years and a mean GFR by 125I-iothalamate clearance of 66.5 +/- 28.3 (range 10-118) ml/min. The iohexol concentrations were measured by a simplified high-performance liquid chromatography method that did not require sample preparation. The iohexol plasma clearance was calculated by both a new one-compartment model as well as by Jacobsson's one-compartment model. Using Jacobsson's single-sample model and data from the 240-min point, there was an excellent correlation between 125 I-iothalamate and nonradioactive iohexol clearance values: r2 = 0.95, standard error of the estimate = 11.4 ml/min, and intrapatient coefficient of variation = 16.9%. However, this formula tended to overestimate GFRs < 30 ml/min and to underestimate GFRs > 80 ml/min. The new one-compartment model is a modification of Bubeck's model, originally used for the determination of renal plasma blood flow. Using this modified model, there was an excellent correlation between 125I-iothalamate and nonradioactive iohexol clearance values at all levels of GFR tested: r2 = 0.95, standard error of the estimate = 9.2 ml/min, and intrapatient coefficient of variation = 13.7%. In conclusion, the determination of the plasma clearance of iohexol by a nonradioactive technique and a monoexponential model is a simple and accurate method of determining the GFR in patients with varying degrees of renal impairment.

Adult↗
PubMed1996

Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats.

Chronic cyclosporin A (CsA) treatment results in major hemodynamic changes in the renal microvasculature and in expression of the intrarenal renin angiotensin system. Changes in renin expression in kidneys of CsA-treated rats include the recruitment of immunoreactive renin in afferent arterioles and in the juxtaglomerular apparatus. This study presents evidence that an acidic isoform of renin is increased in kidneys of CsA-treated rats. Immunoblots of rat kidney homogenate separated by polyacrylamide-gel electrophoresis and also by isoelectric focusing demonstrate the presence of an acidic isoform (pl 5.5 and estimated molecular weight of approximately 32 to 36 kd) seen in increased amounts in kidney homogenate from CsA-treated rats. Silver-stained two-dimensional gels of renin separated from kidney homogenate with pepstatin agarose confirm the presence of an acidic renin isoform in CsA-treated rats. In rats that received CsA for varied intervals of 1, 3, 5, and 8 wk, this acidic isoform is shown to significantly accumulate relative to duration of treatment with CsA when immunoreactive bands are analyzed by densitometric scanning (r2 = 0.90, P < 0.001). Renin enzymatic activity also increased in kidney homogenate of CsA-treated rats relative to duration of treatment with CsA (r2 = 0.486, P < 0.001). Prorenin in these same samples was significantly decreased compared with controls. The acidic renin isoform identified in kidney homogenate of CsA-treated rats may be involved in the vascular changes that are seen in this model.

Acids↗
PubMed1995

Instantaneous and steady-state gains in the tubuloglomerular feedback system.

The load of water and solute entering each nephron of the mammalian kidney is regulated by the tubuloglomerular feedback (TGF) mechanism, a negative feedback loop. Experiments in rats have shown that key variables of this feedback system may exhibit TGF-mediated oscillations. Mathematical modeling studies have shown that the open-feedback-loop gain is a crucial parameter for determining whether oscillations will emerge. However, two different formulations of this gain have been used. The first is the steady-state gain, a readily measurable quantity corresponding to the steady-state reduction in single-nephron glomerular filtration rate (SNGFR) subsequent to a sustained increased in ascending limb flow rate. The second is an instantaneous gain, a variable arising from theoretical considerations corresponding to the maximum reduction in SNGFR resulting from an instantaneous shift of the ascending limb flow column, with the assumption that the SNGFR response is also instantaneous. Here we show by an analytic argument how the steady-state and instantaneous open-feedback-loop gains for the ascending limb are related. In the case of no solute backleak into the ascending limb, the two formulations of gain are equivalent; however, in the presence of solute backleak, the instantaneous gain is larger in magnitude than the steady-state gain. With typical physiological parameters for the rat, calculations with a model previously devised by us show that the gains differ by 5-10%. Hence, experimental measurements of the steady-state gain may provide useful lower-bound estimates of the instantaneous gain of the feedback system in the normal rat. However, the gains may diverge significantly in pathophysiological states where ascending limb transport is compromised by abnormally high NaCl permeability.

Animals↗
PubMed1995

Branching points of renal resistance arteries are enriched in L-type calcium channels and initiate vasoconstriction.

The morphologic structures responsible for the drop in blood pressure along the preglomerular vasculature are not completely defined. Theoretical and videomicroscopic analyses of nonrenal vascular beds implicate bifurcations of resistance arteries as important sites of hemodynamic regulation. These structures contain pacemaker cells sensitive to calcium channel blockers and appear to initiate vasomotion. In the present study, we examined the possibility of functional diversity of smooth muscle cells along resistance arteries with regard to the density of voltage-gated L-type calcium channels. Staining of microdissected renal resistance arteries with Bodipy-labeled dihydropyridine and analysis by confocal microscopy showed enhanced binding at branching points compared with the distal sites in daughter vessels. Antibodies directed against the alpha 1-subunit of the dihydropyridine-sensitive calcium channels confirmed the enhanced expression of L-type channels predominantly at the sites of bifurcations of renal resistance arteries. Fluorescence digital-image analysis of freshly microdissected branches of cortical radial (interlobular) and arcuate arteries intravitally labeled with a calcium indicator, fluo 3, identified branching points as initiator sites of depolarization-induced intracellular Ca2+ concentration ([Ca2+]i) transients, which propagated along the vascular wall at the rate of 2.0 +/- 0.7 micron/s. Videomicroscopy of blood-perfused rat juxtamedullary resistance arteries showed that branching points exhibit more pronounced contractile responses to KCl-induced depolarization than distal sites along the daughter vessels. Collectively, these results demonstrate that branching points are enriched in L-type calcium channels, a finding that suggests these structures may serve as important regulators of renal hemodynamics.

Aniline Compounds↗
PubMed1994

Ascending myogenic autoregulation: interactions between tubuloglomerular feedback and myogenic mechanisms.

A mathematical model of the renal vascular and tubular systems was used to examine the possibility that synergistic interactions might occur between the tubuloglomerular feedback (TGF) and myogenic autoregulatory mechanisms in the kidney. To simulate the myogenic mechanism, the renal vasculature was modelled with a resistance network where the total preglomerular resistance varies with intravascular pressure. In addition, a steady-state model of glomerular filtration, proximal and Henle's loop reabsorption, and TGF-modulation of afferent arteriolar resistance was derived. The results show that, if TGF acts on the distal portion of the preglomerular vasculature, then any TGF-induced vasoconstriction should raise upstream intravascular pressure and, thereby, trigger a myogenic (AMYO) response. The model further predicts that the magnitude of the AMYO response can be similar in magnitude to the TGF-induced increment in afferent resistance. Hence, the effects of TGF excitation on whole kidney hemodynamics may be much greater than predicted from measurements in single nephrons. Moreover, a significant fraction of the intrinsic myogenic autoregulatory response to increased renal perfusion pressure may result from a synergistic interaction between the TGF and myogenic mechanisms.

Arterioles↗
PubMed1994

Numerical simulation of propagating concentration profiles in renal tubules.

Method-dependent mechanisms that may affect dynamic numerical solutions of a hyperbolic partial differential equation that models concentration profiles in renal tubules are described. Some numerical methods that have been applied to the equation are summarized, and ways by which the methods may misrepresent true solutions are analysed. Comparison of these methods demonstrates the need for thoughtful application of computational mathematics when simulating complicated time-dependent phenomena.

Artifacts↗
PubMed1994

Decrease in ambient [Cl-] stimulates nitric oxide release from cultured rat mesangial cells.

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.

Animals↗
PubMed1994

Anatomic pairing of afferent arterioles and renin cell distribution in rat kidneys.

Close afferent arteriolar (AA) connectivity is a prerequisite for hemodynamic interaction between superficial rat nephrons. Studies were conducted in rat, mouse, rabbit, and human renal vasculatures obtained by an HCl maceration-microdissection technique to document the extent of AA connectivity. In rat kidneys, we assessed the possibility for a slow component of internephron coupling, as reflected by arteriolar renin cell distribution after specific immunostaining for renin. In the four species examined, 51% (human) to 60% (mouse) of total AA populations were organized as vascular units consisting of mostly two AA sharing a common origin and a connecting arterial segment. In rat AA pairs, branch lengths were significantly correlated, suggesting coordinated arteriolar growth. The sum of AA branch lengths averaged 278 +/- 6 microns. Rat arteriolar renin status, ranging from no renin cells to renin-recruited midafferent arterioles, distributed in a significantly nonrandom fashion within AA pairs, and 52% of the pairs had equal renin status. Hence, AA pairing is a consistent anatomic characteristic of mammalian kidneys and may constitute an optimal vascular design for hemodynamic as well as endocrine interactions.

Animals↗
PubMed1993

Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney.

To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution of renin and its mRNA was assessed by immunocytochemistry and in situ hybridization. In addition, kidney renin and type 1 angiotensin II (AT1) receptor mRNA levels were determined by Northern blot analysis. The percentage of juxtaglomerular apparatuses containing renin was higher in the CsA (84 +/- 5.5%) than in the Con (61 +/- 6.7%) group, (P < 0.05). The length of renin immunostaining along afferent arterioles was higher in the CsA (74 +/- 4.5 microns) than in the Con (37 +/- 5.1 microns) group, (P < 0.05). In contrast, neither renin mRNA levels nor its intrarenal distribution were altered by chronic CsA administration. Kidney AT1 receptor mRNA levels were lower in the CsA group than in the Con group. We conclude that chronic CsA: (1) induces recruitment of renin containing cells along the afferent arteriole, (2) causes no changes in intrarenal renin mRNA levels or distribution, suggesting that post-transcriptional events may be responsible for the persistence and/or uptake of renin by the preglomerular vasculature, (3) promotes a downregulation of AT1 receptor gene in the kidney, suggesting that local angiotensin II may control AT1 receptor gene expression by a negative feedback.

Animals↗
PubMed1993

Autoregulation of intravascular pressure in preglomerular juxtamedullary vessels.

To quantify the functional significance of autoregulatory responses in preglomerular juxtamedullary (JM) vessels, intravascular pressures (P chi) were measured with a servonull instrument in blood-perfused arcuate (ArcA) and interlobular arteries (ILA), afferent arterioles (AA), and glomerular capillaries (GC) in vitro. P chi was determined at perfusion pressures (Pp) between approximately 60 and 150 mmHg, and the slope of the relationship between Px and Pp was estimated by linear regression. From the regression, Px was 98 +/- 1, 96 +/- 2, 64 +/- 9, and 48 +/- 2 mmHg for ArcA, ILA, AA, and GC, respectively, at the reference perfusion pressure of 100 mmHg. The results show good autoregulation of GC pressure (Pg), with a response slope of 0.10 +/- 0.07 mmHg per mmHg change in Pp, corresponding to an autoregulation index of 0.20 +/- 0.15. The slopes of the Px vs. Pp relationships in ArcA, ILA, and AA were 0.96 +/- 0.02, 0.79 +/- 0.08, and 0.32 +/- 0.11, respectively. To determine whether these observed relationships in preglomerular vessels reflect significant upstream resistance changes, we derived a new autoregulation index for Px measured at an arbitrary preglomerular location. This analysis takes into account the extent to which outflow pressure, Pg, is autoregulated by the ensemble action of the entire preglomerular vasculature. The analysis indicates that 20% autoregulatory compensation occurs upstream from the late ILA, 65% upstream from the late AA, and 80% for the entire preglomerular vascular tree. Hence, in the JM preglomerular circulation, the AA is the major site of autoregulatory resistances adjustment, with a smaller but significant contribution by the ILA.

Animals↗
PubMed1993

Direct visualization of renin-cell distribution in preglomerular vascular trees dissected from rat kidney.

Three methods to visualize directly the distribution of granulated renin-positive cells in vascular trees microdissected from rat kidney were developed. Kidneys were removed from anesthesized rats, hemisectioned, macerated in HCl, and soaked in distilled water for 24-48 h. Cortical preglomerular vascular trees consisting of arcuate and cortical radial arteries and afferent arterioles were microdissected with the aid of a stereomicroscope. Granulated cells can be visualized in three ways. First, under transmitted or incident light observation, granulated cells are readily distinguished from the surrounding smooth muscle cells, because of marked differences in the refractive properties of these two cell types. Second, quinacrine, a fluorescent, intravital stain selective for dense-core granules, can be administered (2 mg/kg iv) to the rat 1 h before nephrectomy. When illuminated with 440-nm light, granulated cells fluorescence strongly at 510 nm. Third, specific immunostaining for renin can be obtained with a polyclonal anti-rat renin antibody and avidin-biotin immunoperoxidase staining in vascular trees subjected to cell permeabilization with Triton. These new techniques permit the direct visualization of the distribution of granulated renin-positive cells in preglomerular vessels under conditions in which the vascular architecture is largely preserved.

Animals↗
PubMed1992

Effect of cyclosporine on endothelial albumin leakage in rats.

Short-term treatment of rats with cyclosporine (cyclosporine A [CsA]; Sandimmune) results in a marked reduction in intravascular plasma volume, a factor that might contribute to the renal dysfunction associated with this potent immunosuppressant. To examine the role of plasma extravasation in CsA-induced hypovolemia, intravascular plasma volumes (PV), blood volumes, [125I]albumin disappearance, and changes in hematocrit (Hct) were measured in Inactin-anesthetized rats subjected to minimal surgery. The rats were treated for 3 wk with either 25 mg/kg/day of CsA s.c. or vehicle. Plasma creatinine and urea were significantly elevated, and magnesium was reduced in the CsA group (N = 6) as compared with controls (CON) (N = 6). CsA treatment had no effect on urinary protein and albumin excretion. Blood volume was significantly lower in CsA than in CON (8.4 +/- 0.5 versus 10.6 +/- 0.3 mL/100 g body wt) as was PV (4.3 +/- 0.2 versus 5.5 +/- 0.2 mL/100 g body wt). Two hours after injection, plasma [125I]albumin concentration had fallen by 41 +/- 4% in CsA versus 23 +/- 5% in CON. Because Hct, and, hence PV, was unchanged in both groups during these 2 h, these data indicate enhanced endothelial albumin leakage in the CsA group. In two additional groups of six rats each, acute volume expansion with fresh whole blood (2 mL/100 g body wt) resulted in extravasation of plasma. Hct rose by 8.0 +/- 0.2% in CsA versus 3.8 +/- 0.2% in CON after 150 min, corresponding to 27 +/- 3 and 15 +/- 2% decreases in total PV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Syncytial organization of cultured rat mesangial cells.

To investigate communication competence of cultured rat mesangial cells, Lucifer yellow transfer was studied using microinjection and scrape-loading techniques. Both methods yielded results indicating considerable gap junctional communication between cultured mesangial cells. Gap junctional communication between mesangial cells was upregulated by adenosine 3',5'-cyclic monophosphate (cAMP). Conversely, cell-to-cell communication was attenuated by exposure to the tumor promoter phorbol myristate acetate, the Ca ionophore ionomycin, reduced oxygen intermediates, and cell acidification. Expression of voltage gated calcium channels by mesangial cells was studied microspectrofluorimetrically using fura-2 fluorescence. KCl-induced depolarization, BAY-K 8644, and readdition of calcium to Ca-free depolarizing medium all produced a nifedipine-inhibitable increase in cytosolic calcium concentration. The existence of voltage-gated calcium channels in communication-competent cells suggests the possibility of propagation of depolarizing signals across the syncytium. This was studied by microapplication of KCl to the microenvironment of a single cell and monitoring fura-2 fluorescence in remote cells. This maneuver resulted in propagating calcium waves in communication-competent monolayers; calcium waves could not be evoked in monolayers exposed to an alkanol-type gap junction uncoupler, octanol. It is concluded that cultured rat mesangial cells form a syncytium capable of propagating calcium transients from a single depolarized cell to its coupled neighbors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Bifurcation analysis of TGF-mediated oscillations in SNGFR.

Recent micropuncture studies in rats have demonstrated the existence of oscillatory states in nephron filtration mediated by tubuloglomerular feedback (TGF). We develop a minimal mathematical model of the TGF system, consisting of a first-order hyperbolic partial differential equation describing thick ascending limb (TAL) NaCl reabsorption and an empirical feedback relation. An analytic bifurcation analysis of this model provides fundamental insight into how oscillatory states depend on the physiological parameters of the model. In the special case of no solute backleak in the TAL, the emergence of oscillations explicitly depends on two nondimensional parameters. The first corresponds to the delay time of the TGF response across the juxtaglomerular apparatus, and the second corresponds to the product of the slope of the TGF response curve at the steady-state operating point and the space derivative of the steady-state NaCl concentration profile in the TAL at the macula densa. Numerical calculations for the case without TAL backleak are consistent with this result. Numerical simulation of the more general case with TAL backleak shows that the bifurcation analysis still provides useful predictions concerning nephron dynamics. With typical parameter values, the analysis predicts that the TGF system will be in oscillatory state. However, the system is near enough to the boundary of the nonoscillatory region so that small changes in parameter values could result in nonoscillatory behavior.

Animals↗