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Biomedical subjects

T Wang

Publications and source records attributed to T Wang.

At least 469 records · Page 26Linked to original sources

Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of blood versus crystalloid cardioplegia.

OBJECTIVES: Blood cardioplegia predominates in the adult because it provides superior myocardial protection, especially in the ischemically stressed heart. However, the superiority of blood over crystalloid cardioplegia in the pediatric population is unproved. Furthermore, because many pediatric hearts undergo a preoperative stress such as hypoxia, it is important to compare the different methods of protection in both normal and hypoxic hearts. METHODS: Twenty neonatal piglets were supported by cardiopulmonary bypass and subjected to 70 minutes of cardioplegic arrest. Of 10 nonhypoxic hearts, five (group 1) were protected with blood cardioplegia and five (group 2) with crystalloid cardioplegia (St. Thomas' Hospital solution). Ten other piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen concentration 8% to 10%) before cardioplegic arrest. Five (group 3) were then protected with blood cardioplegia and the other five (group 4) with crystalloid cardioplegia. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control. Coronary vascular resistance was measured with each infusion of cardioplegic solution. RESULTS: No difference was noted between blood (group 1) or crystalloid cardioplegia (group 2) in nonhypoxic hearts regarding systolic function (end-systolic elastance 104% vs 103%), diastolic stiffness (156% vs 159%), preload recruitable stroke work (102% vs 101%), or myocardial tissue edema (78.9% vs 78.9%). Conversely, in hearts subjected to a hypoxic stress, blood cardioplegia (group 3) provided better protection than crystalloid cardioplegia (group 4) by preserving systolic function (end-systolic elastance 106% vs 40%; p < 0.05) and preload recruitable stroke work (103% vs 40%; p < 0.05); reducing diastolic stiffness (153% vs 240%; p < 0.05) and myocardial tissue edema (79.6% vs 80.1%); and preserving vascular function, as evidenced by unaltered coronary vascular resistance (p < 0.05). CONCLUSION: This study demonstrates that (1) blood or crystalloid cardioplegia is cardioprotective in hearts not compromised by preoperative hypoxia and (2) blood cardioplegia is superior to crystalloid cardioplegia in hearts subjected to the preoperative stress of acute hypoxia.

Animals↗

Prevention of the hypoxic reoxygenation injury with the use of a leukocyte-depleting filter.

OBJECTIVES: Recent studies have shown that an injury occurs when the hypoxic heart is suddenly reoxygenated (as occurs with cardiopulmonary bypass), resulting in myocardial depression, impaired oxygenation, and increased pulmonary vascular resistance. We hypothesize that this injury is, in part, due to oxygen-derived radicals produced by activated white cells and may therefore be ameliorated by limiting leukocytes in the bypass circuit. METHODS: Fifteen neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8% to 10%), followed by reoxygenation with cardiopulmonary bypass at an inspired oxygen fraction of 100% for 90 minutes. In nine piglets (group 1) our routine bypass circuit was used with no modifications, and in six piglets (group 2) a leukocyte-depleting filter (Pall BC-1; Pall Biomedical Products Corporation, Glencoe, N.Y.) was inserted in the arterial line to lower the neutrophil count. Six additional piglets underwent 90 minutes of bypass without hypoxia (cardiopulmonary bypass controls). Postbypass myocardial and pulmonary function was assessed by pressure volume loops, arterial/alveolar ratio, and pulmonary vascular resistance index. Results are expressed as a percentage of control. RESULTS: By comparison with group 1 piglets (reoxygenation without a filter), hypoxic piglets undergoing reoxygenation with a leukocyte-depleting filter (group 2) had improved myocardial systolic function (88% vs 52%; p < 0.05), diastolic compliance (175% vs 275%; p < 0.05), and preload recruitable stroke work (91% vs 54%; p < 0.05); had better preservation of the arterial/alveolar ratio (97% vs 74%; p < 0.05); and had less increase in pulmonary vascular resistance (229% vs 391%; p < 0.05). Furthermore, leukocyte filtration prevented adenosine triphosphate depletion or a change in tissue antioxidants. Conversely, unprotected piglets (group 1) exhibited lower levels of adenosine triphosphate and significant loss of tissue antioxidants. Indeed, the results in the leukocyte-filtered piglets (group 2) were nearly identical to those of piglets subjected to bypass without hypoxia (controls). CONCLUSIONS: (1) This study demonstrates that a major component of the injury that occurs when the hypoxic heart is abruptly reoxygenated is caused by oxygen radicals produced by white blood cells; (2) this injury can be prevented by a leukocyte-depleting filter; and (3) avoidance of this injury improves postbypass myocardial and pulmonary function. These data suggest that leukocyte depletion should be used routinely in all children undergoing operations for cyanotic heart disease or extracorporeal membrane oxygenation.

Adenosine Triphosphate↗

Cardiovascular effects of the fungal extract of basidiomycetes sp. YL8006.

Many fungal products are known to possess biological activity towards the mammalian tissues. We studied vasodilating activity in the crude ethanol extract of the dried mycelia of Basidiomycetes sp. YL8006, cultured by submerged fermentation with a complex medium. The activity was assayed using the isolated perfused rat heart in the working mode. Immediately following injection of the extract into the perfusion system, a 20-25% increase in coronary flow was observed (p<0.001 vs. solvent vehicle control). There was a concurrent decrease in diastolic pressure and coronary vascular resistance. Aortic flow, systolic pressure, and cardiac output declined slightly over time after treatment. No significant changes in heart rate, efficiency, and oxygen consumption were observed. Solvent vehicle did not cause any changes in hemodynamic performance.

Animals↗

Tropomyosin isoforms in nonmuscle cells.

Vertebrate nonmuscle cells, such as human and rat fibroblasts, express multiple isoforms of tropomyosin, which are generated from four different genes and a combination of alternative promoter activities and alternative splicing. The amino acid variability among these isoforms is primarily restricted to three alternatively spliced exon regions; an amino-terminal region, an internal exon, and a carboxyl-terminal exon. Recent evidence reveals that these variable exon regions encode amino acid sequences that may dictate isoform-specific functions. The differential expression of tropomyosin isoforms found in cell transformation and cell differentiation, as well as the differential localization of tropomyosin isoforms in some types of culture cells and developing neurons suggest a differential isoform function in vivo. Tropomyosin in striated muscle works together with the troponin complex to regulate muscle contraction in a Ca(2+)-dependent fashion. Both in vitro and in vivo evidence suggest that multiple isoforms of tropomyosin in nonmuscle cells may be required for regulating actin filament stability, intracellular granule movement, cell shape determination, and cytokinesis. Tropomyosin-binding proteins such as caldesmon, tropomodulin, and other unidentified proteins may be required for some of these functions. Strong evidence for the distinct functions carried out by different tropomyosin isoforms has been generated from genetic analysis of yeast and Drosophila tropomyosin mutants.

Animals↗

The Ca2+ binding protein, frequenin is a nervous system-specific protein in mouse preferentially localized in neurites.

Frequenin is a Ca2+-binding protein that has been implicated in the regulation of neurotransmitter release at the neuromuscular junction [15,16]. However, its cellular and subcellular localization in brain have not been determined. Therefore, we cloned mouse frequenin (Mfreq) and investigated its expression both in vivo and in vitro. The amino acid sequence of Mfreq is homologous to that of frequenins from other species. Northern and Western blot analyses indicated that the Mfreq mRNA is a single species of 4.2 kb, and that the protein has a mass of 24 kDa protein on SDS gel, respectively. Expression of Mfreq is nervous system specific. However, Mfreq mRNA and protein are widely distributed in the brain, spinal cord, and dorsal root ganglia. Mfreq is expressed in early embryonic brain and the levels of Mfreq remain high throughout development. In situ hybridization and immunocytochemistry demonstrated that Mfreq is expressed primarily in neurons and presumptive astrocytes. The Mfreq protein was preferentially localized in neurites (dendrites and axons). Double immunofluorescence microscopy established that Mfreq was co-localized with the dendritic marker, MAP-2 and the synapse marker, SV2 in cultured hippocampal neurons. The distribution and subcellular localization of Mfreq may help understand its cellular function.

Amino Acid Sequence↗

The major soluble tubulins are found in mega dalton (MDa) fractions in fully-grown oocytes and eggs but not in brain of the frog, Rana pipiens.

During progesterone-induced oocyte maturation, the cell is converted from prophase I to metaphase II, which is known to involve microtubule changes. We hypothesize that progesterone affects the polymeric state of tubulins, isoform dynamics, as well as tubulin synthesis and degradation. To test the former, leopard frog (Rana pipiens) oocytes were treated with progesterone, homogenized and centrifuged at 16,000 x g. The resulting pellet and supernatant fractions were analyzed using immunoblots probed with anti-alpha-tubulin antibody DM1A and anti-beta-tubulin antibody DM1B. The results indicate that the majority of tubulins are in supernatant fractions (soluble cellular component) and further indicate changes in size of pelletable tubulins with time post-progesterone treatment. To characterize the supernatant tubulins, Superose-6b columns were used to fractionate 16,000 x g supernatant materials. The results indicate tubulins in fractions of up to 5 MDa (equivalent in size to c. 50 tubulin dimers or 5,000 kDa) predominate, while tubulin dimers and monomers of 110 kDa and 55 kDa, respectively, are relatively minor components. The tubulin in MDa fraction pools in the oocyte soluble component seem to be tissue specific, since the reverse patterns were found in either frog brain or rat (Rattus norvegicus) brain tissue under the same conditions. Microtubule poisons, taxol and nocodazole, were used to test the dynamics of tubulin in MDa fractions and the results were opposite to that expected, i.e., taxol, a microtubule stabilizer, decreased tubulin in large MDa fractions while nocodazole, a microtubule destabilizer, increased it. Preliminary data also indicated that progesterone treatment alters the tubulin size classes (size-shift) in comparison with that in immature oocytes. These results, in combination with other research reports, suggest that tubulin in MDa fractions may either be associated with other cellular components or act as intermediates in microtubule dynamics, perhaps via oligomerization, during oocyte maturation and early development.

Animals↗

Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia.

The neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia. Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.

Antigens↗

Development and validation of a general non-digestive method for the determination of palladium in bulk pharmaceutical chemicals and their synthetic intermediates by graphite furnace atomic absorption spectroscopy.

A simple, selective, sensitive, accurate and relatively inexpensive method for the determination of palladium in bulk pharmaceutical chemicals (BPC) and their synthetic intermediates by graphite furnace atomic absorption spectroscopy has been developed and validated. Sample preparation by direct dissolution of sample in 70% nitric acid is simple and effective without adverse effects. The limit of detection and the limit of quantitation of the method were determined to be 0.7 ppm and 2 ppm respectively in BPC.

Acetates↗

Microinjection of anti-alpha-tubulin antibody (DM1A) inhibits progesterone-induced meiotic maturation and deranges the microtubule array in follicle-enclosed oocytes of the frog, Rana pipiens.

Microinjection of anti-alpha-tubulin (Dm1A) inhibited progesterone-induced meiotic maturation in large follicle-enclosed oocytes of the frog, Rana pipiens. DM1A (46 nl; 10 mg/ml) injection significantly increased the ED50 value for progesterone as determined by germinal vesicle dissolution (GVD) bioassay. By contrast, low doses of microinjected DM1A (46 nl; 2.5 mg/ml), anti-actin (clone KJ43A), anti-cytokeratin (C-11), anti-intermediate filament antibody (IFA), generic IgG (46 nl; 20 mg/ml) or sodium azide (46 nl; 1 mg/ml), an antibody preservative, were without inhibitory effect in this bioassay. Microinjected, affinity-purified DM1A (46 nl; 7.5 mg/ml) was also inhibitory, but preabsorption with pure tubulin prior to injection significantly reduced the inhibitory effect. DM1A injection had no effect on centrifugation-induced germinal vesicle migration (GVM). Previous work indicated that drugs (e.g. demecolcine and nocodazole), which destabilise microtubules, enhance both centrifugation-induced GVM and progesterone-induced GVD in Rana oocytes. Taking these results together, it is suggested that DM1A injection may have differential effects on microtubules in this cell. Thus, while the majority of microtubules were apparently depolymerised by DM1A (46 nl; 10 mg/ml) injection, a small subpopulation appeared to be stabilised as bundles. Confocal immunofluorescence microscopy of follicle-enclosed oocytes after DM1A injection revealed a major loss of microtubules throughout the cell; however, apparent sparse bundles of microtubules arranged in an approximately 600 microns shell were associated with the injectate region 24 h post-injection. By contrast, control follicle-enclosed oocytes topically labelled with DM1A post-fixation had extensive microtubule arrays similar to those previously reported in Xenopus oocytes. Intracellular recording after DM1A injection and progesterone treatment yielded an intermediate membrane potential (Vm = -31.8 mV) compared with control (immature) DM1A-injected cells (Vm = -44.7 mV) or potassium balanced salt solution (KBS)-injected cells matured with progesterone (Vm = -13.9 mV). These results suggest that DM1A injection does not completely inhibit electrophysiological changes initiated by progesterone. Working hypotheses are proposed that suggest a role for microtubules in the action of progesterone which normally lifts the prophase I block in the Rana follicle-enclosed oocyte.

Animals↗

Effect of increased dialysate fill volume on peritoneal fluid and solute transport.

It has recently been recommended that the peritoneal dialysate volume should in general be increased to increase the peritoneal small solute clearances. However, the net ultrafiltration volume may decrease due to higher intraperitoneal hydrostatic pressure (IPP) and higher peritoneal fluid absorption induced by higher fill volume. In the present study, we investigated the effects of increasing the fill volume on peritoneal fluid and solute transport. A four-hour dwell study with frequent dialysate and blood sampling was performed in 32 male Sprague-Dawley rats using 16 ml, 25 ml, 30 ml or 40 ml (8 rats in each group) of 3.86% glucose solution with 131I albumin as an intraperitoneal volume marker. The peritoneal transport of fluid, glucose, urea, sodium, potassium, phosphate and total protein as well as IPP with different fill volume were evaluated. The IPP and peritoneal fluid absorption rate (as estimated from the 131I albumin elimination coefficient, KE) significantly increased with increase in fill volume (P < 0.05), whereas the direct lymphatic absorption did not change with increasing fill volume. There was a strong correlation between IPP and KE. However, the net ultrafiltration volume was significantly higher in the high fill volume groups compared to the low fill volume groups, mainly due to a better maintenance of the dialysate to plasma glucose concentration gradient in the high fill volume groups. There was no significant difference in the diffusive mass transport coefficients (KBD) and sieving coefficients for any of the investigated solutes, although KBD values tended to be lower in the 16 ml group. The clearances for small solutes increased with increased fill volume, although these increases were slightly smaller than predicted from the increase in fill volume. We conclude that: (1) An increase in dialysate fill volume using 3.86% glucose solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption, but, on the other hand, a higher net ultrafiltration; (2) The increase in net ultrafiltration with increased fill volume is mainly due to a better maintenance of glucose concentration in the dialysate, inducing an increased transcapillary ultrafiltration rate; (3) Solute clearances increase although not quite to the same extent as predicted from the increase in fill volume. Our results indicate that decreased net ultrafiltration volume associated with higher dialysate fill volume (due to higher IPP and higher peritoneal fluid absorption) could be avoided if hypertonic glucose solutions are used.

Animals↗

A quantitative analysis of sodium transport and removal during peritoneal dialysis.

To quantitatively evaluate peritoneal sodium transport, the diffusive mass transport coefficient (KBD) and sieving coefficient (S), as well as the mass of sodium transported by diffusion (DM), by convection (CM) and by fluid absorption (AM) and the total sodium mass removed (RM) were calculated during a series of single dwell studies in CAPD patients. A six-hour dwell study was performed in 68 patients using 2 liter of 1.36% (N = 13), 2.27% (N = 9) or 3.86% (N = 46) glucose dialysis fluid with 131I-albumin as the intraperitoneal volume marker. The patients in whom the 3.86% glucose dialysis fluid was applied were further divided into four transport groups according to a modified peritoneal equilibration test: high (H), high-average (H-A), low-average (L-A), and low (L) transport. There was no significant difference in KBD nor in S for sodium among different solutions. However, the removed sodium mass (RM) was significantly higher in the 3.86% (70.5 +/- 31.5 mmol) and 2.27% (36.0 +/- 21.0 mmol) solutions as compared to that of the 1.36% (-1.8 +/- 26 mmol) solution mainly due to increased both CM and DM. In general, CM was twice as high as DM. AM substantially decreased sodium removal. Among the different transport groups, the KBD and S values for sodium were significantly higher in the H group as compared to the other transport groups (both P < 0.05). However, RM was significantly lower in the H group mainly due to higher AM. Using a 3.86% glucose solution, the D/P for sodium was found to be significantly different (but only after 120 min of the dwell) between all the different transport groups. In conclusion, sodium removal in CAPD is strongly related to the fluid removal. The ultrafiltration induced convective transport (CM) and peritoneal absorption of sodium (AM) were of similar magnitude and were twice as high as the diffusive transport (DM) and both play an important role in the peritoneal sodium balance. A D/P for sodium using the 3.86% glucose solution, especially at the end of the dwell, can be used to discriminate between different transport categories of patients. High transport patients have a poor fluid and sodium removal that are likely to affect their clinical outcome.

Biological Transport↗

An encapsulation system for the immunoisolation of pancreatic islets.

Over a thousand combinations of polyanions and polycations were tested to search for new polymer candidates that would be suitable for encapsulation of living cells. The combination of sodium alginate, cellulose sulfate, poly (methylene-co-guanidine) hydrochloride, calcium chloride, and sodium chloride was most promising. In parallel, a novel multiloop chamber reactor was developed to control the time of complex formation and to negate gravitational effects such as pancreatic islet sedimentation and droplet deformation during the encapsulation process. Encapsulated rat islets demonstrated glucose-stimulated insulin secretion in vitro, and reversed diabetes in mice. This new capsule formulation and encapsulation system allows independent adjustments of capsule size, wall thickness, mechanical strength, and permeability, which may offer distinct advantages for immunoisolating cells.

Animals↗

Mutations synthetically lethal with tpm1delta lie in genes involved in morphogenesis.

Yeast contains two genes, TPM1 and TPM2, encoding tropomyosins, either of which can provide an essential function in the yeast cytoskeleton. To elucidate more clearly the function of the major tropomyosin, encoded by TPM1, we have isolated mutations that confer synthetic lethality with the null mutant of TPM1. Here we describe a phenotypic and genetic analysis of mutations in TSL1/BEM2, TSL2, TSL3, TSL5, and TSL6 (tropomyosin synthetic lethal). All the mutants exhibit clear morphological and some actin cytoskeletal defects, but are not noticeably defective in secretion, endocytosis, or organelle segregation. The lethality conferred by tsl tpm1delta mutations could be specifically suppressed by either TPM1 or an additional copy of TPM2. This implies that the essential function compromised in the tsl tpm1delta constructs is the same essential function for which Tpm1p or Tpm2p is necessary. Synthetic interactions and unlinked noncomplementation were observed between the tsl mutants, suggesting that they participate in related functions involving morphogenesis. In support of this, tsl6-1 was identified as an allele of the nonessential gene SLT2 or MPK1 whose product is a MAP kinase regulating cell wall synthesis. These results indicate that this synthetic lethality approach provides a sensitive screen for the isolation of mutations affecting morphogenesis, many of which are likely to be in nonessential genes, like BEM2 and SLT2.

Actins↗

Dioctyl sodium sulphosuccinate increases net ultrafiltration in peritoneal dialysis.

BACKGROUND: The surface-active substance dioctyl sodium sulphosuccinate (DSS) has been reported to increase the peritoneal clearances of urea and creatinine. This study investigated the effects of DSS on the fluid and solute transport characteristics of the peritoneum. DESIGN: A 4-h single-dwell experiment session of peritoneal dialysis using 25 ml of 3.86% glucose dialysis solution with an intraperitoneal volume maker was performed in 16 male Sprague-Dawley rats. In eight rats, 0.005% (50 p.p.m.) DSS was added to the dialysis fluid. No DSS was given to the other eight rats (control group). The transport of fluid, glucose, potassium, sodium, urea, phosphate and urate were analysed. RESULTS: There was a significant increase in the intraperitoneal volume in the DSS group. At 240 min, the drain volume in DSS group (33.0 +/- 2.9 ml) was significantly higher compared to the control group (28.8 +/- 2.1 ml, P < 0.01). This increase in the drain volume was mainly due to a decrease in peritoneal fluid absorption rate in the DSS group (0.040 +/- 0.013 ml/min) as compared to the control group (0.054 +/- 0.010 ml/min, P < 0.05). There was no significant difference in the diffusive permeability and sieving coefficient for the small solutes between these two groups. However, the clearances for urea and sodium were higher in the DSS group, mainly due to the increase in the dialysate volume. CONCLUSION: Our results suggest that DSS significantly increases the net ultrafiltration of peritoneal dialysis. This effect, which was mainly due to a decrease in the fluid absorption rate, contributed to the increased clearances for urea and sodium. DSS did not alter the diffusive permeability and sieving coefficient for the small solutes.

Animals↗

Identification and characterization of three new promoter/operators from Corynebacterium diphtheriae that are regulated by the diphtheria toxin repressor (DtxR) and iron.

DtxR is a dimeric, sequence-specific, DNA-binding protein that functions as an iron-dependent, negative global regulator in Corynebacterium diphtheriae. Under high-iron conditions, DtxR represses the synthesis of diphtheria toxin, corynebacterial siderophore, and other components of the high-affinity iron uptake system. Three DtxR-regulated promoter/operators designated tox, IRP1, and IRP2 were reported previously. In this study, we identified and characterized three additional DtxR-regulated promoter/operators from C. diphtheriae designated IRP3, IRP4, and IRP5. When beta-galactosidase was expressed from these three new promoter/ operators in Escherichia coli containing dtxR+ on pDSK29, enzyme levels were 5- to 30-fold lower during high-iron growth than during low-iron growth. In gel shift assays, the mobility of DNA fragments containing each promoter/operator decreased in the presence of purified DtxR and Co2+. In footprinting assays, DtxR protected 36-, 35-, and 30-bp regions of IRP3, IRP4, and IRP5, respectively, from cleavage by DNase I. In the 19-bp core of each promoter/operator, 12 or 13 bp matched the consensus for the DtxR-binding site. The putative polypeptides encoded by the open reading frames (ORFs) downstream from IRP3 and IRP4 were homologous, respectively, to several bacterial transcriptional regulators and to the deduced polypeptide encoded by an ORF located between the E. coli genes for primosomal replication protein N and adenine phosphoribosyltransferase. The putative polypeptide encoded by the ORF downstream from IRP5 was not homologous to any sequence in the protein database at the National Center for Biotechnology Information. When the ORFs downstream from IRP3 and IRP4 were expressed under the control of the phage T7 promoter in E. coli, polypeptide products of the predicted sizes were detected in small amounts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Amino Acid Sequence↗

Differential effects of dorsomedial medulla lesion size on ingestive behavior in rats.

Previous studies indicate that rats with lesions centered on the area postrema (AP) drink more saline and consume abnormally large amounts of water after treatment with subcutaneous isoproterenol (Iso) angiotensin II. In addition, lesioned rats lose a significant amount of body weight immediately after surgery. Nonetheless, there are disparate reports on the effects of lesions of the AP on fluid intake and body weight. These reports suggest that the adjacent nucleus of the solitary tract (NTS) may play a role in the effects observed subsequent to the lesion. In this study we evaluated the effects of varying lesion size on body weight, fluid intake, and the baroreflex. As the lesion included more of the NTS, the effect on body weight was reduced. Moreover, water intake induced by Iso increased as more NTS was involved in the lesion. Conversely, 3-h ad libitum saline intake and saline intake after sodium depletion decreased with more involvement of the NTS in the lesion. These data suggest that the neural population in the NTS bordering the AP may play a critical role in the control of water and saline intake as well as the regulation of body weight.

Animals↗

Nitric oxide regulates HCO3- and Na+ transport by a cGMP-mediated mechanism in the kidney proximal tubule.

The effects of nitric oxide (NO) on blood pressure and renal hemodynamics are well established, but those of NO on renal tubule HCO3- and Na+ transport are not fully understood. In this study, we combined renal clearance and in situ microperfusion techniques to investigate the effects of NO on the renal excretion of Na (FE(Na%)) and the rates of renal tubule absorption of fluid (J(V)) and bicarbonate (J(HCO3)) in the rat kidney. Administration of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg iv bolus) did not change mean blood pressure and glomerular filtration rate significantly. However, L-NAME significantly increased urine flow rate and FE(Na%), and these effects were maintained over a 60-min period. Addition of L-NAME markedly decreased both J(V) and J(HCO3) in the proximal tubule. In contrast, addition of 1 microM sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) significantly increased both J(V) and J(HCO3). Similar stimulation was also observed when 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 1 microM) was added to the luminal perfusate. The stimulatory effects of SNP and 8-BrcGMP on J(V) and J(HCO3) were not additive. The increments in J(V) and J(HCO3) due to SNP were abolished by the Na+/H+ exchange blocker ethylisopropylamiloride and the guanylate cyclase inhibitor methylene blue. These results indicate that NO stimulates proximal tubule Na+ and HCO3- transport through a cGMP-linked pathway in the kidney proximal tubule.

Absorption↗