Biomedical subjects

C T Wang

Publications and source records attributed to C T Wang.

At least 19 recordsLinked to original sources

PubMed2001

A plant gene encoding a Myb-like protein that binds telomeric GGTTTAG repeats in vitro.

A gene (AtTRP1) encoding a telomeric repeat-binding protein has been isolated from Arabidopsis thaliana. AtTRP1 is a single copy gene located on chromosome 5 of A. thaliana. The protein AtTRP1 encoded by this gene is not only homologous to the Myb DNA-binding motifs of other telomere-binding proteins but also is similar to several initiator-binding proteins in plants. Gel retardation assay revealed that the 115 residues on the C terminus of this protein, including the Myb motif, are sufficient for binding to the double-stranded plant telomeric sequence. The isolated DNA-binding domain of AtTRP1 recognizes each telomeric repeat centered on the sequence GGTTTAG. The almost full-length protein of AtTRP1 does not form any complex at all with the DNA fragments carrying four or fewer GGTTTAG repeats. However, it forms a complex with the sequence (GGTTTAG)(8) more efficiently than with the sequence (GGTTTAG)(5). These data suggest that the minimum length of a telomeric DNA for AtTRP1 binding consists of five GGTTTAG repeats and that the optimal AtTRP1 binding may require eight or more GGTTTAG repeats. It also implies that this protein AtTRP1 may bind in vivo primarily to the ends of plant chromosomes, which consist of long stretches of telomeric repeats.

Amino Acid Sequence↗

PubMed2001

Genetic parameters of reproductive traits in Brown Tsaiya ducks artificially inseminated with semen from Muscovy drakes.

A selection experiment on maximum duration of fertility of Brown Tsaiya ducks after artificial insemination (AI) with pooled Muscovy semen has been conducted since 1992. The Brown Tsaiya ducks were divided into two lines: a control line (T) with no selection and a selected line (S). The traits measured were the number of eggs set that were laid from Days 2 to 15 after one AI (NES), the number of fertile eggs at candling (NEF), the total number of dead embryos (NED), the maximum duration of fertility (MD), and the number of hatched mule ducklings (NEH). The selected trait was NEF. Six generations with a total of 2,127 females were measured. The variance components were estimated for each line in a multiple-trait animal model, using the restricted maximum likelihood (REML) methodology, which yields estimates free of bias caused by selection and inbreeding. Estimates of the heritability and genetic correlation from the two lines were very similar. Heritabilities in the S and T lines, respectively, were 0.14 and 0.10 for NES, 0.30 and 0.26 for NEF, 0.06 and 0.09 for NED, 0.28 and 0.21 for MD, and 0.18 and 0.19 for NEH. High and favorable genetic correlations existed between NEF and MD (0.96 and 0.92), between NEF and NEH (0.86 and 0.91), and between MD and NEH (0.90 and 0.82). The results suggested that selection for NEF could improve the maximum duration of fertility, but it could be useful to check the estimates of genetic parameters in a meat-type female duck.

Animals↗

PubMed2001

Cellular membrane-binding ability of the C-terminal cytoplasmic domain of human immunodeficiency virus type 1 envelope transmembrane protein gp41.

The amphipathic alpha-helices located in the cytoplasmic tail of the envelope (Env) transmembrane glycoprotein gp41 of human immunodeficiency virus type 1 have been implicated in membrane association and cytopathicity. Deletion of the last 12 amino acids in the C terminus of this domain severely impairs infectivity. However, the nature of the involvement of the cytoplasmic tail in Env-membrane interactions in cells and the molecular basis for the defect in infectivity of this mutant virus are still poorly understood. In this study we examined the interaction of the cytoplasmic tail with membranes in living mammalian cells by expressing a recombinant cytoplasmic tail fragment and an Escherichia coli beta-galactosidase/cytoplasmic tail fusion protein, both of them lacking gp120, the gp41 ectodomain, and the transmembrane region. We found through cell fractionation, in vivo membrane flotation, and confocal immunofluorescence studies that the cytoplasmic tail contained determinants to be routed to a perinuclear membrane region in cells. Further mapping showed that each of the three lentivirus lytic peptide (LLP-1, LLP-2, and LLP-3) sequences conferred this cellular membrane-targeting ability. Deletion of the last 12 amino acids from the C terminus abolished the ability of the LLP-1 motif to bind to membranes. High salt extraction, in vitro transcription and translation, and posttranslational membrane binding analyses indicated that the beta-galactosidase/LLP fusion proteins were inserted into membranes via the LLP sequences. Subcellular fractionation and confocal microscopy studies revealed that each of the LLP motifs, acting in a position-independent manner, targeted non-endoplasmic reticulum (ER)-associated beta-galactosidase and enhanced green fluorescence protein to the ER. Our study provides a basis for the involvement of the gp41 cytoplasmic tail during Env maturation and also supports the notion that the membrane apposition of the C-terminal cytoplasmic tail plays a crucial role in virus-host interaction.

Animals↗

PubMed2001

Arterial tissue of arsenic, selenium and iron in Blackfoot disease patients.

In order to identify arsenic as one of the major factors that cause Blackfoot disease on the southwest coast of Taiwan, an atomic absorption spectrophotometric method was used to determine arsenic, selenium and iron concentrations in the tissue of plantar digital arteries. Samples from 31 patients with Blackfoot disease and 30 controls with road traffic accident or occupational injuries were studied. The results indicate that the arterial tissue from Blackfoot disease patients had higher arsenic concentration (3.06+/-1.42 microg/g) than that from healthy controls (0.59+/-0.28 microg/g). The variability was very large 418% at p<0.001. It was also noted that the concentrations of selenium (1.23+/-0.41 microg/g and 1.05+/-0.13 microg/g in patients and controls respectively; with variability 17.1%) and iron (72.7+/-34.9 microg/g and 35.2+/-16.5 microg/g in patients and controls respectively; with variability 106.5%) were both higher than those of controls. However, only the iron concentration was significantly different (p<0.05).

Arsenic↗

PubMed2001

[Detection of the wheat salt-tolerant-mutant using PCR-SSCP combining with direct sequenceing].

gf-2.8 is a gene located on the chromosomal homologous group 4, which was reported to have relationship with salt tolerance of wheat. A pair of primers were designed to amplify the coding region of gf-2.8 in the two salt-tolerant mutants and their parents. Agarose gel electrophoresis showed that the 685 bp band was amplified among all the materials. SSCP analysis suggested that 974915 (one of the mutants) was different from the other materials. The sequencing results showed that Jimai 24 and its salt-tolerant mutant 8901-17 had the same sequence as published, which indicated that the mutation site of 8901-17 was not on the gf-2.8 gene. However, there were at least two single base mutations in the gf-2.8 of 974915, one of which caused the alternation of amino acid, this mutation occurred in the conservative region of gf-2.8.

Base Sequence↗

PubMed2000

Renormalization group analysis for thermal turbulent transport.

In this study, we continue with our previous renormalization group analysis of incompressible turbulence, aiming at determination of various thermal transport properties. In particular, the temperature field T is considered a passive scalar. The quasinormal approximation is assumed for the statistical correlation between the velocity and temperature fields. A differential argument leads to derivation of the turbulent Prandtl number Pr(t) as a function of the turbulent Peclet Pe(t) number, which in turn depends on the turbulent eddy viscosity nu(t). The functional relationship between Pr(t) and Pe(t) is comparable to that of Yakhot et al. [Int. J. Heat Mass Transf. 30, 15 (1987)] and is in close consistency with direct-numerical-simulation results as well as measured data from experiments. The study proceeds further with limiting the operation of renormalization group analysis, yielding an inhomogeneous ordinary differential equation for an invariant thermal eddy diffusivity sigma. Simplicity of the equation renders itself a closed-form solution of sigma as a function of the wave number k, which, when combined with a modified Batchelor's energy spectrum for the passive temperature T, facilitates determination of the Batchelor constant C(B) and a parallel Smagorinsky model and the model constant C(P) for thermal turbulent energy transport.

Journal Article↗

PubMed2000

Assembly and release of human immunodeficiency virus type 1 Gag proteins containing tandem repeats of the matrix protein coding sequences in the matrix domain.

We have constructed human immunodeficiency virus (HIV) gag mutants by increasing the matrix protein (MA) sequences via tandemly repeated duplication of the central 107-MA codons. Instead of a total of 132 amino acid residues for the wild-type MA, the resultant mutants designated as MA2, MA3, and MA4 contained a total of 242, 352, and 462 codons in the MA domains, respectively. Analysis indicated that the addition of 110 or 220 amino acid residues to the MA did not significantly affect the assembly, release, and processing of particles; however, particle production was markedly reduced when another copy of 110 residues was added to the MA. Subcellular fractionation analysis suggested that the MA tandem repeat mutations enhanced the Gag membrane affinity, in a manner which correlated with the copy number of MA sequences. The effects of enhanced membrane affinity were substantially reduced when sequences downstream of the capsid (CA) domain were deleted. Sucrose density gradient fractionation analysis showed that particles produced by the large insertion mutants possessed wild-type (wt) HIV particle density. Truncation of sequences downstream of the nucleocapsid (NC) domains of the mutants did not influence the budding of particles. In contrast, particle budding was severely impaired when sequences downstream of the CA domain were truncated. Particle densities for the large Gag proteins, which were truncated at the C-terminus of CA, were about 1.12-1.14 g/ml lower than that for wt. Our results suggest that the HIV MA domain could adopt insertions of large protein sequences, and strongly support the proposal that the NC and p2 domains play a crucial role in the process of correct Gag protein packing.

Cell Line↗

PubMed2000

Multimerization potential of the cytoplasmic domain of the human immunodeficiency virus type 1 transmembrane glycoprotein gp41.

We previously demonstrated that an envelope mutant of human immunodeficiency virus type 1 lacking the entire cytoplasmic domain interferes in trans with the production of infectious virus by inclusion of the mutant envelope into the wild-type envelope complex. We also showed that the envelope incorporation into virions is not affected when the wild-type envelope is coexpressed with the mutant envelope. These results suggest that an oligomeric structure of the cytoplasmic domain is functionally required for viral infectivity. To understand whether the cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein gp41 has the potential to self-assemble as an oligomer, in the present study we fused the coding sequence of the entire cytoplasmic domain at 3' to the Escherichia coli malE gene, which encodes a monomeric maltose-binding protein. The expressed fusion protein was examined by chemical cross-linking, sucrose gradient centrifugation, and gel filtration. The results showed that the cytoplasmic domain of gp41 assembles into a high-ordered structural complex. The intersubunit interaction of the cytoplasmic domain was also confirmed by a mammalian two-hybrid system that detects protein-protein interactions in eucaryotic cells. A cytoplasmic domain fragment expressed in eucaryotic cells was pulled down by glutathione-Sepharose 4B beads via its association with another cytoplasmic domain fragment fused to the C terminus of the glutathione S-transferase moiety. We also found that sequences encompassing the lentiviral lytic peptide-1 and lentiviral lytic peptide-2, which are located within residues 828-856 and 770-795, respectively, play a critical role in cytoplasmic domain self-assembly. Taken together, the results from the present study indicate that the cytoplasmic domain of gp41 by itself is sufficient to assemble into a multimeric structure. This finding supports the hypothesis that a multimeric form of the gp41 cytoplasmic domain plays a crucial role in virus infectivity.

ATP-Binding Cassette Transporters↗

PubMed2000

Analysis of a human immunodeficiency virus type 1 gag mutant with an engineered 110-amino-acid insertion in the matrix protein domain.

A human immunodeficiency virus (HIV) matrix (MA) protein mutant was constructed by duplication of 107 codons of the HIV-1 MA domain. This MA protein duplication mutant (MAII) still could assemble and process particles, had a wild-type (wt) HIV particle density, and possessed reverse transcriptase activity of about 80% of the wild type virus level. The incorporation of HIV Env and viral RNA genome was not greatly affected. The MAII was noninfectious or poorly infectious, however, when pseudotyped with an amphotropic murine leukemia virus envelope protein or with the HIV envelope protein. Although the MAII mutant displayed an immunofluorescence staining pattern similar to that of the wild type virus, subcellular fractionation studies indicated that the membrane association of MAII Gag precursors was unstable under high-salt conditions. Electron microscopic studies showed that the mutant had a decreased density of particle cores compared with that of the wild type virus, suggesting an altered arrangement of the packed proteins. As this insertion in the MA gene caused no major effects on virus assembly implies that the HIV-1 gag has the potential to adapt large insertions of extra coding sequences without loss of the ability to direct particle assembly and release.

Blotting, Western↗

PubMed2000

Assembly and processing of human immunodeficiency virus Gag mutants containing a partial replacement of the matrix domain by the viral protease domain.

We constructed human immunodeficiency virus (HIV) mutants by replacing the matrix domain with sequences encoding the viral protease or p6* and protease. The chimeras retaining matrix myristylation and processing signals underwent efficient autoprocessing with severely defective particle budding. The budding defects of the chimeras were rescued by suppressing the chimera protease activity either through addition of an HIV protease inhibitor or through inactivating the chimera protease via a substitution mutation of the catalytic aspartic acid residue. This resulted in the release of chimeric virus-like particles with the density of a wild-type retrovirus particle. In addition, the assembly-competent but processing-defective chimeras produced proteolytically processed particles with significant reverse transcriptase activity when a downstream native pol gene was present. These results suggest that HIV has the potential to adapt heterologous sequences in place of the matrix sequence without major effects on virus-like particle budding. In addition, the positions of the protease and substrate accessibility may contribute significantly toward avoiding a premature Gag or Gag-Pol process, which leads to severe defects in both particle budding and incorporation.

Amino Acid Sequence↗

PubMed2000

Impairment of pressure-natriuresis and renal autoregulation in ANG II-infused hypertensive rats.

Chronic infusions of initially subpressor doses of angiotensin II (ANG II) lead to progressive hypertension over a 2-wk period and to augmented intrarenal ANG II levels. The present study was performed to investigate total renal blood flow (RBF) and medullary blood flow (MBF) autoregulatory behavior and pressure-natriuresis in ANG II-infused hypertensive rats and how these are modified by concomitant treatment with an ANG II AT(1) receptor antagonist. ANG II-infused rats (n = 27) were prepared by administration of ANG II at 60 ng/min via osmotic minipump for 13 days. Twelve of the ANG II-infused hypertensive rats were treated with losartan in the drinking water (30 mg. kg.(-1) day(-1)). Rats were anesthetized with pentobarbital sodium (50 mg/kg, ip) and prepared for renal function measurements. An aortic clamp was placed above the junction of the left renal artery to reduce renal arterial pressure. Autoregulatory responses for renal plasma flow, overall RBF, and glomerular filtration rate were impaired in ANG II-infused hypertensive rats; however, MBF autoregulation was not disrupted. Most strikingly, pressure-natriuresis was markedly suppressed in ANG II-infused hypertensive rats. Chronic treatment with losartan prevented the impairment of the pressure-natriuresis relationship caused by chronic ANG II infusion. These findings demonstrate that chronic ANG II infusion leads to marked impairment of sodium excretion and suppression of the pressure-natriuresis relationship, which may contribute to the progressive hypertension that occurs in this model. These renal effects are prevented by simultaneous treatment with an AT(1) receptor blocker.

Angiotensin II↗

PubMed2000

Mycobacterial infection of the upper extremities.

BACKGROUND AND PURPOSE: Mycobacterial infection of the upper extremities is extremely rare. To make an early accurate diagnosis is often difficult, and the treatment is, therefore, frequently delayed in clinical practice. This paper describes the diagnosis and treatment of mycoabacterial infection of the upper extremities in a series of patients treated at National Taiwan University Hospital. METHODS: The medical records of 15 patients with mycobacterial infection of the upper extremities treated between 1985 and 1998 were retrospectively analyzed. The diagnosis of mycobacterial infection was established by positive culture results, the presence of acid-fast bacilli, or characteristic histopathologic findings. RESULTS: Mycobacterial infection was suspected on initial examination in only two patients. The duration between the onset of symptoms and correct diagnosis averaged 37.5 months (range, 3 wk to 209 mo). The involved sites of mycobacterial infection included the wrist in nine patients, the elbow in two, the hand in two, the humerus in two, the forearm in one, and the shoulder in one. Three patients suffered from multifocal musculoskeletal mycobacterial infection. Microbiologic studies identified Mycobacterium tuberculosis in four patients and nontuberculous mycobacteria (NTM) in four. Characteristic histopathologic findings of mycobacterial infection including caseation, granulomatous inflammation, eosinophilic epithelioid cells, Langhan's giant cells, and lymphocytic aggregates were noted in all 15 patients. All patients received chemotherapy and 14 patients underwent surgical treatment. The mean duration of follow-up was 46 months (range, 15-97 months). Treatment failed in two of the patients with multifocal NTM infection and in one patient whose mycobacterial infection was identified by histopathology. CONCLUSIONS: Mycobacterial infection should be included in the differential diagnosis of infection of the upper extremities. Treatment failures are more frequent in patients with multifocal NTM infection.

Adolescent↗

PubMed1999

Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets.

Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3beta,15alpha-diacetoxy-26-oic acid], isolated from the Chinese medicinal fungus Ganoderma lucidum (Fr.) Karst (Polyporaceae), exerted a concentration-dependent inhibition on the response of human gel-filtered platelets (GFP) to U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2alpha), a thromboxane (TX) A2 mimetic. GAS at 2 microM inhibited 50% of cell aggregation. GAS at 7.5 microM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of alpha-granule secretion, and over 95% of aggregation. GAS also strongly inhibited U46619-induced diacylglycerol formation, arachidonic acid release, and TXB2 formation. An immunoblotting study of protein-tyrosine phosphorylation showed that GAS inhibited the formation of phosphotyrosine proteins at the steps involving the engagement of integrin alphaIIbbeta3 and aggregation. However, GAS did not inhibit U46619-induced platelet shape change or the inhibitory effect of U46619 on the prostaglandin E1-evoked cyclic AMP level in GFP. It is concluded that GAS inhibits platelet response to TXA2 on the receptor-Gq-phospholipase Cbeta1 pathway, but not on the receptor-G1 pathway.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1999

Predominant inhibition of ganodermic acid S on the thromboxane A2-dependent pathway in human platelets response to collagen.

Ganodermic acid S (GAS), a membrane acting agent, exerts multiple effects on human platelet function (C.N. Wang et al. (1991) Biochem. J. 277, 189-197). The study reported how GAS affected the response of human gel-filtered platelets (GFP) to collagen. The agent inhibited cell aggregation by prolonging lag and shape change periods and decreasing the initial cell aggregation rate. However, the inhibitory efficiency was less than its inhibition on GFP response to U46619, a thromboxane (TX) A2 mimetic. In the agent-effect on biochemical events, GAS effectively inhibited Ca2+ mobilization, phosphorylation of myosin light chain, dense granule secretion and TXB2 generation. The inhibitions might originate from blocking Ca2+ mobilization of the TXA2-dependent pathway. GAS partially decreased the phosphorylation of most phosphotyrosine proteins from early activation to the integrin alphaIIbbeta3-regulated steps. The agent did not affect the phosphorylation of three proteins at the steps regulated by integrin alphaIIbbeta3. The results suggest that GAS inhibits the collagen response predominantly on the TXA2-dependent signaling, and the tyrosine kinase-dependent pathway in collagen response plays a major role in aggregation.

Blood Platelets↗

PubMed1999

Cation permeability and cation-anion interactions in a mutant GABA-gated chloride channel from Drosophila.

To investigate the structural basis of anion selectivity of Drosophila GABA-gated Cl(-) channels, the permeation properties of wild-type and mutant channels were studied in Xenopus oocytes. This work focused on asparagine 319, which by homology is one amino acid away from a putative extracellular ring of charge that regulates cation permeation in nicotinic receptors. Mutation of this residue to aspartate reduced channel conductance, and mutation to lysine or arginine increased channel conductance. These results are consistent with an electrostatic interaction between this site and permeating anions. The lysine mutant, but not the arginine mutant, formed a channel that is permeable to cations, and this cannot be explained in terms of electrostatics. The lysine mutant had a 25-mV reversal potential in solutions with symmetrical Cl(-) and asymmetrical cations. The permeability ratio of K(+) to Cl(-) was determined as 0. 33 from reversal potential measurements in KCl gradients. Experiments with large organic cations and anions showed that cation permeation can only be seen in the presence of Cl(-), but Cl(-) permeation can be seen in the absence of permeant cations. Measurements of permeability ratios of organic anions indicated that the lysine mutant has an increased pore size. The cation permeability of the lysine-containing mutant channel cannot be accounted for by a simple electrostatic interaction with permeating ions. It is likely that lysine substitution causes a structural change that extends beyond this one residue to influence the positions of other channel-forming residues. Thus protein conformation plays an important role in enabling ion channels to distinguish between anions and cations.

Amino Acid Sequence↗

PubMed1999

Heritabilities and genetic correlations of body weights and feather length in growing Muscovy selected in Taiwan.

1. Heritabilities and genetic correlations in the base population of a closed strain of Muscovy duck, moderately selected for body weight at 10 weeks of age, have been estimated from the data of 9 successive generations for the following traits: male and female body weight at 10 and 18 weeks of age (BW10m, BW18m, BW10f, BW18f) and length of the 8th primary feather at 10 weeks of age (F110m, F110f). 2. Multivariate REML with an animal model was used, pooling data from the 9 generations (3283 and 3289 male and female offspring respectively). The same trait expressed in male and female was considered as 2 different traits. 3. The 8th primary feather was longer in females than in males by 6% to 22% at 10 weeks of age. Body weight was heavier in males than in females by 42% to 58% at 10 weeks of age and by 57% to 75% at 18 weeks of age. 3. The heritability estimates for body weight traits showed moderate values, being a little higher for females than for males at the same age, increasing with age from h2=0.24 at BW10m to h2=0.43 at BW18f. 4. The heritability estimates for feather length showed that a greater response would be obtained in selection for male feather length (h2=0.37) than for female length (h2=0.14). Both have high genetic correlations with body weight so they could be indirectly improved. 5. Heritabilities of the difference in body weights between males and females at 10 weeks (h2=0.07) and 18 weeks of age (h2=0.10) were small, as well as for feather length (h2=0.10). It would probably be difficult to modify sexual dimorphism in body weight through selection. 6. Genetic correlations between BW10m, BW18m and BW10f, BW18f were respectively r(g)=0.77 and r(g)=0.80. They were larger for body weight at the same ages between males and females, r(g)=0.90 (r(g)=0.88 between F110m and F110f). Body weight in males and females at the same age should be better considered as 2 different traits in a selection programme. 7. The cumulated predicted genetic gains expressed per unity of the genetic standard deviation (sigma(g)) over the 8 generations of selection were 1.3 sigma(g) and 1.4 sigma(g) respectively for the BW10m and BW10f. The predicted correlated responses were 1.2 sigma(g) for body weights at 18 weeks of age, 0.9 sigma(g) and 0.7 sigma(g) for F110f and F110m respectively.

Animals↗

PubMed1999

Proximal tubular angiotensin II levels and renal functional responses to AT1 receptor blockade in nonclipped kidneys of Goldblatt hypertensive rats.

-Previous studies have shown that whereas the nonclipped kidney in two-kidney, one clip (2K1C) rats undergoes marked depletion of renin content and renin mRNA, intrarenal angiotensin II (Ang II) levels are not suppressed; however, the distribution and functional consequences of intrarenal Ang II remain unclear. The present study was performed to assess the plasma, kidney, and proximal tubular fluid levels of Ang II and the renal responses to intrarenal Ang II blockade in the nonclipped kidneys of rats clipped for 3 weeks. The Ang II concentrations in proximal tubular fluid averaged 9.19+/-1.06 pmol/mL, whereas plasma Ang II levels averaged 483+/-55 fmol/mL and kidney Ang II content averaged 650+/-66 fmol/g. Thus, as found in kidneys from normal rats with normal renin levels, proximal tubular fluid concentrations of Ang II are in the nanomolar range. To avoid the confounding effects of decreases in mean arterial pressure (MAP), we administered the nonsurmountable AT1 receptor antagonist candesartan directly into the renal artery of nonclipped kidneys (n=10). The dose of candesartan (0.5 microg) did not significantly decrease MAP in 2K1C rats (152+/-3 versus 148+/-3 mm Hg), but effectively prevented the renal vasoconstriction elicited by an intra-arterial bolus of Ang II (2 ng). Candesartan elicited significant increases in glomerular filtration rate (GFR) (0.65+/-0. 06 to 0.83+/-0.11 mL. min-1. g-1) and renal blood flow (6.3+/-0.7 to 7.3+/-0.9 mL. min-1. g-1), and proportionately greater increases in absolute sodium excretion (0.23+/-0.07 to 1.13+/-0.34 micromol. min-1. g-1) and fractional sodium excretion (0.38+/-0.1% to 1.22+/-0. 35%) in 2K1C hypertensive rats. These results show that proximal tubular fluid concentrations of Ang II are in the nanomolar range and are much higher than can be explained on the basis of plasma levels. Further, the data show that the intratubular levels of Ang II in the nonclipped kidneys of 2K1C rats remain at levels found in kidneys with normal renin content and could be exerting effects to suppress renal hemodynamic and glomerular function and to enhance tubular reabsorption rate.

Angiotensin I↗

PubMed1999

Intrarenal angiotensin II generation and renal effects of AT1 receptor blockade.

The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal function and the pathophysiology of hypertension. Angiotensin II (AngII) is formed intrarenally from systemically delivered angiotensin I (AngI) and intrarenally formed AngI. Intrarenal AngII content, which is greater than can be explained by the circulating AngII concentrations, is compartmentalized such that proximal tubule concentrations of AngI and AngII greatly exceed plasma concentrations. Proximal tubule cells are thought to secrete AngII or precursors of AngII into the tubular fluid to activate luminal AngII receptors. Recent immunohistochemical studies have demonstrated an abundance of AT1 receptors on the luminal surface of proximal and distal tubule cells and on afferent and efferent arteriolar vascular smooth muscle cells and mesangial cells of glomeruli. Activation of luminal AT1 receptors stimulates tubular sodium reabsorption rate. To evaluate the direct effects of AT1 receptor blockade on renal function in AngII-dependent hypertension, experiments were performed on two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Although the nonclipped kidney is renin-depleted, the intrarenal AngII levels are not suppressed, and AngII concentrations in proximal tubular fluid remain high (10(-8) M). Candesartan was administered into the renal artery of nonclipped kidneys to avoid the confounding consequences of decreases in arterial pressure. Blockade of intrarenal AT1 receptors elicited significant increases in GFR, renal blood flow, sodium excretion, and fractional sodium excretion, suggesting synergistic actions on tubular transport and vascular smooth muscle cells.

Angiotensin I↗