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PubMed1994

Development and validation of a monoclonal antibody enzyme immunoassay for measuring progesterone in saliva.

A nonextraction, competitive, solid-phase enzyme immunoassay with a monoclonal antibody was developed and validated for measuring progesterone in saliva. The antibody was raised against 11 alpha-hydroxyprogesterone hemisuccinate-bovine serum albumin conjugate and was indirectly immobilized to the walls of microtiter wells. The labeled analyte (progesterone-horseradish peroxidase conjugate) was homologous with the immunogen. The lower detection limit (concentration equivalent to B0-3 SD) was 38 pmol/L of saliva sample. We validated the assay with studies to establish the independence of the concentration determined from the volume of saliva assayed, quantitative recovery of progesterone added to saliva, interference from possible cross-reactants, and agreement with a similar assay that incorporated an extraction step. In addition, we determined luteal-phase concentrations of salivary progesterone in normal women and compared the results with those of an older assay involving a polyclonal antibody.

Antibodies, Monoclonal↗
PubMed1997

Rapid analytical tryptic mapping of a recombinant chimeric monoclonal antibody and method validation challenges.

A rapid and reproducible analytical tryptic mapping method was developed as an identity test for a recombinant chimeric monoclonal antibody for lot release testing. The unfolding, reduction, carboxymethylation, trypsin digestion, and reversed-phase (RP) HPLC steps were optimized to provide a reproducible method. The optimized method requires 30 min for unfolding the protein, 30 min for carboxymethylation, 4 h for digestion with TPCK-trypsin and 140 min for RPHPLC analysis. The total time required is less than 8 h compared to conventional procedures, which must be performed over several days. The optimized method was validated for its precision, recovery, specificity, and robustness. The precision of the method was determined by repeatability and intermediate precision experiments. Relative standard deviation (RSD) values were < or = 10% for the relative peak areas of marker peaks. The mean recovery of these marker peaks was 88.4%. The specificity was demonstrated by the unique tryptic mapping patterns obtained compared with several other monoclonal antibodies. Robustness was demonstrated by the relative insensitivity of the tryptic map to small deliberate changes in key method parameters. Excessive relative peak area variability observed for one peak (RSD 52%) was traced to adsorption to glass autosampler vials. This variability was substantially reduced (RSD 11%) by substituting polypropylene autosampler vials. The data demonstrate that this method may be applicable to a wide range of pharmaceutically relevant monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed2002

Importance of the detection method for thyroglobulin antibodies for the validity of thyroglobulin measurements in sera from patients with Graves disease.

BACKGROUND: The use of recovery tests has been proposed to disclose interferences from anti-thyroglobulin antibodies (TgAbs) in thyroglobulin (Tg) assays. We studied the value of a recovery test in Tg measurement by a new commercial IRMA. METHODS: Blood samples were collected from 153 patients with untreated Graves disease. Tg and TgAbs were measured by IRMA and RIA, respectively (Dynotest Tg-plus and Dynotest anti-Tgn; Brahms Diagnostica). The recoveries of added amounts of Tg were calculated for each serum. RESULTS: TgAbs were detected in 72 of the 153 patients (47%). The recovery test results for the 81 TgAb-negative sera (median, 101%; range, 80-115%) were identical to the results for the 91 controls (median, 102%; range, 80-124%). By contrast, significantly lower recovery test results were observed for the 72 TgAb-positive sera (median, 79%; range, 60-103%; Z = -8.363; P <0.0001). In the 34 of the 72 TgAb-positive sera with a normal recovery test, Tg concentrations were significantly lower (median Tg, 13.6 microg/L; range, 1.1-360 microg/L) than those measured in the TgAb-negative sera (median, 107 microg/L; range, 1.2-700 microg/L; Z = -3.797; P <0.0001). CONCLUSIONS: Tg values were decreased in TgAb-positive sera even when the results of the recovery tests were normal. This test should not be used alone to determine the validity of a serum Tg measurement in Graves disease.

Adolescent↗
PubMed2004

The intracellular antibody capture technology: towards the high-throughput selection of functional intracellular antibodies for target validation.

Several approaches have been developed over the past decade to study the complex interactions that occur in biological system. The ability to carry out a comprehensive genetic analysis of an organism becomes more limited and difficult as the complexity of the organism increases because complex organisms are likely to have not only more genes than simple organisms but also more elaborate networks of interactions among those genes. The development of technologies to systematically disrupt protein networks at the genomic scale would greatly accelerate the comprehensive understanding of the cell as molecular machinery. Intracellular antibodies (intrabodies) can be targeted to different intracellular compartments to specifically interfere with function of selected intracellular gene products in mammalian cells. This technique should prove important for studies of mammalian cells, where genetic approaches are more difficult. In the context of large-scale protein interaction mapping projects, intracellular antibodies (ICAbs) promise to be an important tool to knocking out protein function inside the cell. In this context, however, the need for speed and high throughput requires the development of simple and robust methods to derive antibodies which function within cells, without the need for optimization of each individual ICAb. The successful inhibition of biological processes by intrabodies has been demonstrated in a number of different cells. The performance of antibodies that are intracellularly expressed is, however, somewhat unpredictable, because the reducing environment of the cell cytoplasm in which they are forced to work prevents some antibodies, but not others, to fold properly. For this reason, we have developed an in vivo selection procedure named Intracellular Antibody Capture Technology (IACT) that allows the isolation of functional intrabodies. The IAC technology has been used for the rapid identification of antigen-antibody pairs in intracellular compartments and for the in vivo identification of epitopes recognized by the selected intracellular antibodies. Several optimizations of the IAC technology for protein knock-out have been developed so far. This system offers a powerful and versatile proteomic tool to dissect diverse functional properties of cellular proteins in different cell lines.

Animals↗
PubMed2001

Validity of specific IgE antibodies in children with egg allergy.

BACKGROUND: The demonstration of specific IgE antibodies to egg supports the existence of allergy to this food, but a correct diagnosis can only be obtained after a challenge test. Several studies have assessed different cut-off points in the level of these antibodies as predictors of clinical reactivity. OBJECTIVE: Validation of the specific IgE antibodies measured by the CAP System Fluorescence enzyme immunoassay (FEIA) technique in the diagnosis of egg allergy in children under 2 years of age. METHODS: A prospective study of 81 children with suspected egg allergy was performed. Specific IgE antibodies was quantified for egg white, egg yolk, ovoalbumin and ovomucoid. The diagnostic challenge test was carried out following the previously established criteria. The validity of the specific IgE antibodies was analysed using children with a negative diagnostic challenge test as control group. RESULTS: The prevalence of egg allergy in the group studied was 79% and egg white was the allergen that showed the greatest diagnostic efficacy. The sensitivity and positive predictive value of the prick test and of the CAP to egg white were excellent and the specificity and the negative predictive value had lower values. A level of > or = 0.35 KU(A)/L for specific IgE antibodies to egg white predicted the existence of reaction in 94% of the cases. CONCLUSIONS: Quantification of the specific IgE antibodies to egg white is useful in the diagnosis of egg allergy. In children under 2 years of age with a background of immediate hypersensitivity after egg ingestion and presence of specific IgE antibodies to egg white of > or = 0.35 KU(A)/L, diagnostic challenge test is not necessary to establish the diagnosis of allergy to this food.

Antibody Specificity↗
PubMed1998

Validation of antibody-based recognition by piezoelectric transducers through electroacoustic admittance analysis.

The development of immunosensors based on piezoelectric transducers is widely investigated due to their attractive potentialities. The quartz crystal microbalance (QCM) may give a direct response signal which characterizes the binding event between a sensitive layer, immobilized onto the surface transducer, and the analysis to be detected. However, for small biomolecules, such as some antigens, it is quite difficult to obtain an observable signal. This is mainly due to the lack of sensitivity of the commonly used QCM (5 to 10 MHz quartz crystal). Moreover, the mass estimated with the QCM response through the Sauerbrey equation and the mass which can be measured thanks to other analytical techniques, in our case an enzymatic assay, are different: the deposited mass is generally overestimated by the QCM. To validate QCM mass measurements and, therefore antigens recognition, the interactions of acoustic shear waves with a biolayer were investigated during enzyme adsorption onto the microbalance gold electrode or during the antibody/antigen binding. Electroacoustic admittance was measured around the resonance frequency of a 27 MHz quartz resonator in parallel with microbalance measurements. The parameters which characterize the quartz microbalance equivalent circuit were compared with the classical microbalance frequency. The mass overestimation, given by the microbalance, could be explained either by modification of the rheological properties of the sensitive layers and/or by an inadequacy of the assay performed.

Acoustic Impedance Tests↗
PubMed1993

Analysis of active antibody concentration. Separation of affinity and concentration parameters.

Antibody binding to surfaces with differing amounts of immobilised antigen was measured in a biosensor system using surface plasmon resonance detection. Binding rates obtained during the initial binding phase on high density antigen surfaces were proportional to antibody concentration and independent of antigen-antibody affinity. One antibody calibration curve covering the range from 0.5 to 160 nM (0.08-25 micrograms/ml) antibody was valid for IgG antibodies with different antigen specificities. To illustrate the use of this methodology active antibody concentrations were analysed in culture media and in rabbit serum.

Animals↗
PubMed1994

Semi-preparative purification and validation of monoclonal antibodies for immunotherapy in mice.

A number of rat hybridomas were adapted to grow in RPMI containing either 5% IgG-depleted FCS or 1% serum-free Nutridoma. Alternatively, protein-free Ultradoma PF was used. Growth in these media allowed purification procedures to be used that are based on tangential ultrafiltration in combination with affinity chromatography on gels linked to protein G or anti-rat L chain coupled antibodies. The isolated antibody preparations were found to be pure and to consist of monomeric intact IgG. The yield and recovery of mAb using this procedure were found to be consistently high. These antibody preparations were analyzed for endotoxin contamination. Whereas during isolation endotoxin contamination increased, the endotoxin content per mg purified protein did not. Affinity chromatography on Detoxi-gel resulted in the efficient removal of this contamination and using this protocol the antibody preparations obtained were found to be of sufficient purity, activity and low endotoxin content to permit their in vivo use in animal models of immunotherapy.

Animals↗
PubMed1992

Excessive production of transforming growth-factor beta 1 can play an important role in the development of tumorigenesis by its action for angiogenesis: validity of neutralizing antibodies to block tumor growth.

Angiogenesis is an important part of tumor growth in vivo. We used the transfected Chinese hamster ovary (CHO) cells that overproduced recombinant transforming growth-factor beta 1 (TGF-beta 1) to examine the possible role of this factor in tumor growth and angiogenesis in a nude mouse model. The in-vitro proliferation of TGF-beta 1-transfected CHO cells was unaffected by the treatment of either recombinant TGF-beta 1 or an anti-TGF-beta 1 antibody. The TGF-beta 1-transfected cells grew more rapidly than the parental CHO cells when injected subcutaneously into nude mice. The tumors derived from the TGF-beta 1-transfected cells showed prominent tumor-associated angiogenesis, whereas the parental cells produced tumors without such angiogenesis. In addition, an anti-TGF-beta 1 neutralizing antibody was able to inhibit both growth and angiogenesis in the tumors derived from TGF-beta 1-transfected cells. These findings suggest that the overproduction of TGF-beta 1 by tumor cells can contribute to neovascularization and may help promote tumor development in vivo.

Animals↗
PubMed1998

Adaptation and validation of antibody-ELISA using dried blood spots on filter paper for epidemiological surveys of tsetse-transmitted trypanosomosis in cattle.

The indirect enzyme-linked immunosorbent assay (ELISA) for the detection of anti-trypanosomal antibodies in bovine serum was adapted for use with dried blood spots on filter paper. Absorbance (450 nm) results for samples were expressed as percent positivity, i.e. percentage of the median absorbance result of four replicates of the strong positive control serum. The antibody-ELISA was evaluated in Zambia for use in epidemiological surveys of the prevalence of tsetse-transmitted bovine trypanosomosis. Known negative samples (sera, n = 209; blood spots, n = 466) were obtained from cattle from closed herds in tsetse-free areas close to Lusaka. Known positive samples (sera, n = 367; blood spots, n = 278) were obtained from cattle in Zambia's Central, Lusaka and Eastern Provinces, diagnosed as being infected with Trypanosoma brucei, T. congolense, or T. vivax using the phase-contrast buffy-coat technique or Giemsa-stained thick and thin blood smears. For sera (at a cut-off value of 23.0% positivity) sensitivity and specificity were 86.1 and 95.2%, respectively. For bloodspots (at a cut-off value of 18.8% positivity) sensitivity and specificity were 96.8 and 95.7%, respectively. The implications of persistence of antibodies following treatment or self-cure are discussed.

Animals↗
PubMed2002

[Unusual manifestations of autoimmune thyroiditis].

Autoimmune thyroid disease (AITD) is quite common and comprises goitrous and nongoitrous eu- and hypothyroid Hashimoto's Disease with or without preceding thyrotoxicosis, classical hyperthyroid Graves' Disease and its rarer eu- and hypothyroid variants. There is no generally accepted international classification of AITD. Important aspects of the pathogenesis of AITD have been elucidated in the past two decades. AITD may be explained by an excess of either stimulating and/or destructive/blocking immune processes or by a balanced coexistence of various of these pathological autoimmune features. The HLA (DQA1*0501) is involved in determining the susceptibility to AITD. The measurement of antibodies against thyroidal peroxidase and TSH receptor has become the cornerstone in the diagnosis of AITD. Antibodies directed against TSH receptors are stimulating (TSAb) or blocking (TSBAb). In routine measurements they are determined by a radioligand assay which does not distinguish between these two different types of antibodies. A valid interpretation of antibody results is therefore only possible in connection with the clinical findings and the results of thyroid hormone measurements. We present here four unusual cases with AITD which illustrate its complexity and summarize the present state of knowledge on this disease.

Adult↗
PubMed2002

Validation of monoclonal antibody F99/97.6.1 for immunohistochemical staining of brain and tonsil in mule deer (Odocoileus hemionus) with chronic wasting disease.

A new monoclonal antibody (MAb), F99/97.6.1, that has been used to demonstrate scrapie-associated prion protein PrP(Sc) in brain and lymphoid tissues of domestic sheep with scrapie was used in an immunohistochemistry assay for diagnosis of chronic wasting disease (CWD) in mule deer (Odocoileus hemionus). The MAb F99/97.6.1 immunohistochemistry assay was evaluated in brain and tonsil tissue from 100 mule deer that had spongiform encephalopathy compatible with CWD and from 1,050 mule deer outside the CWD-endemic area. This MAb demonstrated abnormal protease-resistant prion protein (PrP(res)) in brains of all of the 100 mule deer and in 99 of the 100 tonsil samples. No immunostaining was seen in samples collected from deer outside the endemic area. MAb F99/97.6.1 demonstrated excellent properties for detection of PrP(res) in fresh, frozen, or mildly to moderately autolytic samples of brain and tonsil. This immunohistochemistry assay is a sensitive, specific, readily standardized diagnostic test for CWD in deer.

Animals↗
PubMedDate not supplied

[Validity of antigliadin antibodies in the diagnosis of celiac disease].

Antibodies to gliadin, detected by immunofluorescence (IFL-AGA) and ELISA (ELISA-AGA), have been found in 68 of 71 (96%) sera from children with active celiac disease. AGA of IgA class were confined to celiac disease on normal diet and after gluten challenge, as all the antibodies, found in children on gluten free diet (40%) and in control gastroenterological diseases (20%), were of IgG class. Sera from 175 first-degree relatives of our celiacs were also screened for AGA. IFL-AGA were positive in 13 (7%) and ELISA-AGA in 27 cases (15%). Antibodies were of IgA class in 13 relatives (7%). A celiac's asymptomatic sister, selected for jejunal biopsy only on the basis of IgA AGA positivity, showed subtotal villous atrophy. Although AGA cannot replace jejunal biopsy in the diagnosis of celiac disease, they can be regarded as useful tools in the screening of gluten sensitive enteropathy. Moreover, as a positive IgA AGA test is closely related to the active phases of celiac disease, their research can be useful both to evaluate the effect of gluten free diet and to establish when a new biopsy is appropriate after gluten challenge.

Adolescent↗
PubMed1996

Genital chlamydial infection among women in Nicaragua: validity of direct fluorescent antibody testing, prevalence, risk factors and clinical manifestations.

OBJECTIVE: To validate the performance of a direct fluorescence antibody (DFA) test and to determine the prevalence, risk factors and clinical manifestations of cervical chlamydia infection in different groups of women in Nicaragua. STUDY POPULATION: 926 women, 863 routine clinic attenders (mean age 27 years) and 63 sex workers (mean age 25 years) attending health centres in León, Corinto, Matagalpa and Bluefields. METHODS: Cervical specimens were examined using the Syva MicroTrak test system with a cut-off of 10 or more elementary bodies (EBs). The DFA results were validated by a one-step polymerase chain reaction (PCR) assay. Discordant results were further examined in nested PCR assays directed at two different target genes. An interviewer-administered questionnaire and a standard gynaecological examination were completed. RESULTS: Sensitivity of DFA was 80.1%, specificity 98.3%, and positive and negative predictive values 62.5% and 99.3%, respectively. Values were lower in locations where samples thawed because of electricity breaks and higher among sex workers. The majority of discordant results was confirmed as positive in nested PCR assays. Prevalence of cervical chlamydia infection based on positivity in DFA and/or PCR ranged from 2% among routine clinic attenders aged 35 years or older, to 8% among adolescent clinic attenders, and to 14% among sex workers. Among routine clinic attenders, young age (odds ratio [OR] 3.6, 95% confidence intervals [95% CI] 1.4-8.9 for women aged 15-19 years as compared with 1 in women 25 years of age or older) and use of oral contraceptives (OR 4.0, 95% CI 1.7-9.6) were the only statistically significant risk factors identified in multivariate logistic regression analysis. Presence of mucopurulent cervical discharge (OR 5.9, 95% CI 3.0-11.5) and presence of ectropion (OR 2.6, 95% CI 1.1-6.5) were the clinical signs independently associated with infection. CONCLUSIONS: Our results indicate that the DFA test was sensitive and specific while the performance of the PCR assay depends on adequate storage of samples. Genital C trachomatis infection is a common health problem among women in Nicaragua. The wide implementation of syndromic STD management algorithms together with health education programmes aimed at young people is the most promising approach to control STD in Nicaragua.

Adolescent↗
PubMed2005

90Y Labeling of monoclonal antibody MOv18 and preclinical validation for radioimmunotherapy of human ovarian carcinomas.

The monoclonal antibody (mAb) MOv18 binds the membrane alpha isoform of the folate receptor (FR) which is overexpressed in human ovarian carcinoma cells. Exploiting the targeting capacity of this mAb, we developed and preclinically validated a protocol for the stable labeling of the mAb with 90Y, an isotope which has shown promise in cancer radioimmunotherapy. MOv18 was derivatized with the stable macrocyclic ligand p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (Bz-DOTA). MOv18-Bz-DOTA conjugates were labeled with 90Y or 111In under metal-free and good laboratory practice conditions. At the optimal Bz-DOTA/mAb derivatization ratio of 4-5, conjugates maintained binding activity up to 6 months, were efficiently labeled with 90Y or 111In (mean labeling yield 85 and 64%, associated to a final mean specific activity of 74 and 37 MBq/mg) and displayed a mean immunoreactivity of 60 and 58%, respectively. The radiolabeled preparations were stable in human serum, with >97% radioactivity associated to mAb at 48 h after labeling. The ability of 90Y- and 111In-MOv18 to localize FR on tumors in vivo was analyzed in nude mice bearing tumors induced by isogenic cell lines differing only in the presence or absence of the relevant antigen [A431FR (FR-positive) and A431tMock (FR-negative)]. In vivo biodistribution in organs other than tumor was comparable in non-tumor-, A431tMock- and A431FR-bearing mice, whereas the median tumor uptake of the radiolabeled reagents, expressed as area under the curve (AUC) and maximum uptake (Umax), was significantly higher (sixfold to sevenfold) in A431FR than in A431tMock tumors (P=0.0465 and P=0.0332, respectively). Mean maximum uptake (% ID/g) for 90Y-MOv18 was 53.7 and 7.4 in A431FR and A431tMock respectively; corresponding values for 111In-Mov18 were 45.0 and 11.3. These data demonstrate the feasibility of 90Y-labeling of MOv18 without compromising antibody binding ability and the immunoreagent-specific localization in vivo on FR-expressing tumors, suggesting the suitability of 90Y-MOv18 for clinical studies.

Antibodies, Monoclonal↗
PubMed2004

[Clinical validity of anti-thyroperoxidase antibody and anti-thyroglobulin antibody].

OBJECTIVE: To evaluate the clinical validity of anti-thyroperoxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb). METHOD: Serum levels of anti-TPOAb and anti-TgAb were assayed using chemiluminescence immunoassay in 434 subjects, including 51 patients with Hashimoto's thyroiditis, 58 with Graves' disease, 68 with nodular goiter, 56 with thyroid adenoma and carcinoma, 56 with subacute thyroiditis, 65 with euthyroid non-thyroid endocrine disease, 35 with euthyroid non-thyroid autoimmune diseases, and 45 euthyroid controls. RESULTS: The highest level and most positive results of serum anti-TgAb and anti-TPOAb were observed in patients with Hashimoto's thyroiditis (median 373 and 6 974 U/ml, positive rate 84.3% and 86.3%), followed by patients with Graves' disease (median 84 and 1 369 U/ml, positive rate 44.8% and 72.4%). Serum anti-TgAb and anti-TPOAb were also more common in patients with subacute thyroiditis and other autoimmune diseases than in the controls. CONCLUSION: The assay of serum anti-TPOAb and anti-TgAb by chemiluminescence immunoassy are useful in the differential diagnosis of autoimmune thyroid disease.

Adenoma↗
PubMed2003

Validity of a rapid assay for antisperm antibodies in semen.

OBJECTIVE: To determine the validity of a rapid assay for antisperm antibodies in semen. DESIGN: Prospective comparison of the results of standard and rapid antisperm antibody assays performed simultaneously. SETTING: Tertiary care infertility center. PATIENT(S): Couples who presented for infertility evaluation. INTERVENTION(S): Semen analysis and measurement of antisperm antibodies in semen using a standard and a rapid immunobead binding test (IBT). MAIN OUTCOME MEASURE(S): [1] Comparison of sperm parameters between semen-containing antisperm antibodies and semen free of antisperm antibodies. [2] Validation of the rapid test by calculation of sensitivity, specificity, positive and negative predictive values of the rapid assay using the standard assay as a gold standard. [3] Cost comparison of the standard and rapid test. RESULT(S): [1] Nine semen specimens with antisperm antibodies had a significantly lower sperm concentration, motility, and total motile fraction compared to 44 specimens without antisperm antibodies. Also, specimens with antisperm antibodies had a significantly higher percentage of vibratory sperm and percent of bound antisperm antibodies. The strict morphology, liquefaction time, semen volume, and white blood cell concentration were no different between the two groups. [2] Using a threshold of > or =12% of bound antisperm antibodies in the rapid assay, the sensitivity, specificity, positive and negative predictive values of the test are 100% when correlated with a threshold of > or =20% in the standard assay. Increasing the threshold in the standard assay decreases the specificity and positive predictive value of the rapid assay but not the sensitivity and the negative predictive value. [3] The cost of the rapid assay was 16% that of the standard test and its performance took 20% of the time it took to set and perform the standard test. CONCLUSION(S): A rapid test for antisperm antibodies is valid, reliable, and more cost and labor effective than a standard IBT.

Autoantibodies↗
PubMed1989

Antihypertensive mechanism of captopril in renal hypertensive rats: studies with a nonpeptide angiotensin II receptor antagonist and an angiotensin II monoclonal antibody.

The validity of using EXP6803, a nonpeptide angiotensin II (AII) receptor antagonist, and KAA8, an AII monoclonal antibody, as specific tools for studying the physiology of AII has been established previously. In this study, we used these specific probes to examine the role of blocking AII formation in the antihypertensive effect of captopril in conscious renal artery-ligated rats (RALRs), a high renin, renal hypertensive model. Mean arterial pressure and plasma renin activity in a typical group of RALRs averaged 175 +/- 5 mm Hg and 28.2 +/- 6.2 ng of angiotensin 1 per ml/hr (n = 6), respectively. The antihypertensive effect of captopril (3 mg/kg i.v.) was determined in RALRs given either EXP6803 (30 mg/kg + 2 mg/kg/min i.v.) or KAA8 (10 mg + 1 mg/min i.v. per rat) with the corresponding vehicle-treated RALRs. These doses of EXP6803 and KAA8 were very effective in blocking the pressor response to AII but not to norepinephrine or vasopressin in RALRs. Captopril decreased mean arterial pressure by 44 +/- 2 and 53 +/- 8 mm Hg in the groups treated with the vehicles of EXP6803 (n = 5) and KAA8 (n = 5), respectively. In the presence of EXP6803 (n = 5) or KAA8 (n = 5), the antihypertensive effect of captopril was almost or totally abolished. Indomethacin did not alter the antihypertensive effect of captopril. These results suggest that the antihypertensive effect of captopril in conscious RALRs is due mainly to the blockade of AII formation. Furthermore, circulating AII rather than locally formed AII appears to play a major role in maintaining hypertension in hypertension in RALRs.

Angiotensin II↗