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1.
Journal of China Pharmaceutical University ; (6): 185-192, 2020.
Article in Chinese | WPRIM | ID: wpr-821082

ABSTRACT

@#To study the inhibitory effect of celastrol respectively combined with glycyrrhetic acid, paclitaxel, and rhein on the proliferation of human hepatoma cell line HepG2. The MTT method was used to detect the survival rate of HepG2 cells. The cooperativity index(CI)and Jin′s formula method were used to determine the synergistic effect. Apoptosis and cell cycle arrest were detected, too. The results show that celastrol, glycyrrhetinic acid, rhein, and paclitaxel alone can inhibit the proliferation of HepG2 cells, respectively. Combination with glycyrrhetic acid, paclitaxel, and rhein, respectively, the inhibitory effect of celastrol on the proliferation of HepG2 cells was significantly enhanced. And the synergistic effect on the proliferation inhibition of HepG2 cells in some concentrations was displayed in the experiment. The cell apoptosis rate was improved(P< 0. 01)and more cells were arrested in G2/M phase. Celastrol respectively combined with glycyrrhetic acid, paclitaxel, and rhein displayed a synergistic inhibitory effect on the proliferation of HepG2 cells, and the effect was related to inducing cell apoptosis and increasing the cell cycle arrest in G2/M phase.

2.
China Pharmacy ; (12): 1655-1660, 2019.
Article in Chinese | WPRIM | ID: wpr-817116

ABSTRACT

OBJECTIVE: To establish content determination method of Triptolide-glycyrrhetic acid compound microemulsion, optimize the formula and investigate its physicochemical properties and release rate in vitro. METHODS: The content of Triptolide- glycyrrhetic acid compound microemulsion was determined by UPLC. The determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1% formic acid aqueous solution-acetonitrile (gradient elution) at the flow rate of 0.4 mL/min. The column temperature was 40 ℃. The detection wavelength was set at 218 nm, and sample size was 5 μL. Pseudo-ternary phase diagrams were drawn by water titration method. Using oil phase, surfactants and co-surfactants as index, the formula was optimized, and in intro release characteristics was investigated by in vitro release test. RESULTS: The linear range of triptolide and glycyrrhetinic acid were 1-40 μg/mL(r=0.999 7) and 10-400 μg/mL(r=0.999 8), respectively. The limits of quantitation were 0.5 and 0.8 μg/mL; the limits of detection were 0.1 and 0.2 μg/mL. RSDs of precision, stability and reproducibility tests were all less than 2%. Average recoveries were 100.32%-101.15% (RSD=0.36%, n=6), 99.78%-101.42% (RSD=0.59%,n=6). The optimal formula included that medium chain triglyceride as oil phase, polyethylene glycol hydroxy stearate as surfactants, ethanol as co-surfactants, water as water phase, the proportion of them was 8 ∶  28 ∶ 14 ∶ 50. The obtained microemulsion was O/W type, being transparent and clear, with average diameter, average polydispersity index and average viscosity of (62.38±3.44) nm, 0.096±0.001 and (26.84±1.10) mPa·S. Within 24 h, cumulative release rates of triptolide and glycyrrhetinic acid in obtained microemulsion were 99.8% and 99.7% (in PBS pH 2.0), 99.3% and 99.4% (in PBS pH 7.4), 98.9% and 98.4% (in PBS pH 9.0), respectively. Triptolide and glycyrrhetinic acid released faster in the single microemulsion than in the compound microemulsion. CONCLUSIONS: Established content determination method is simple and stable. The optimized formula is stable and feasible. Obtained iriptolide-glycyrrhetinic acid compound microemulsion show better sustained-release effect than sigle microemulsion.

3.
Int. arch. otorhinolaryngol. (Impr.) ; 21(4): 390-398, Oct.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-892821

ABSTRACT

Abstract Introduction This study is a systematic review on recent developments about the importance of HMGB1 protein in the pathogenesis of rhino-sinusal inflammatory diseases. We also report data on the use of 18-β-glycyrrhetic acid (GA), which has been shown able to inhibit the pro-inflammatory activities of HMGB1, in young patients affected by allergic rhinitis and complaining of nasal obstruction as main symptom. Objectives The objective of this study was to review the literature to demonstrate the importance of HMGB1 in the pathogenesis of nasal inflammatory disorders and understand whether the inhibition of this protein may be an efficacious and innovative therapeutic strategy for patients with rhino-sinusal inflammation. Data Synthesis Authors searched for pertinent articles indexed in PubMed, Scopus, and other health journals between 2004 and 2015. In total, the authors gathered 258 articles: 219 articles through Pubmed and 39 articles from other search engines. The search terms used were as follows: HMGB1 AND "respiratory epithelium," "airway inflammation," "rhinitis," "allergic rhinitis," "rhinosinusitis," "nasal polyposis," "glycyrrhetic acid," "children." Conclusions Patients with severe symptoms have the highest serum levels and the highest extracellular expression of HMGB1. GA inhibits HMGB1 chemotactic and mitogenic function by a scavenger mechanism on extracellular HMGB1 accumulation stimulated by lipopolysaccharides in vitro. Treatment of allergic rhinitis with GA is not associated with local or systemic side effects in children and adults.

4.
Chinese Traditional and Herbal Drugs ; (24): 1740-1747, 2017.
Article in Chinese | WPRIM | ID: wpr-852805

ABSTRACT

Objective: To analyze the components exposing in rat plasma after oral administration of Baoerkang Powder, and to study the mechanism of Baoerkang Powder and pharmacokinetic behavior. Methods: Components absorbed in rat plasma after oral administration of Baoerkang Powder to rats were analyzed by UPLC tandem High-resolution mass spectrometer. The structures of Baoerkang Powder in rat plasma identified by comparing the retention time, molecular weight, and CID fragmentation patterns with their corresponding compounds reported in the literatures. Results: Twenty-three components in rat plasma were identified after oral administration of Baoerkang Powder to rats for 1 h, including five components confirmed by comparing retention time and information of mass with their reference substances, components confirmed were vitexin, liquiritigenin, hesperetin, glycyrrhetic acid, and ursolic acid. Conclusion: It is suggested that the method could be applied to quick analysis of the components exposing in rat plasma after oral administration of Baoerkang Powder, which is beneficial to studying its mechanism and pharmacokinetic behavior.

5.
Chinese Traditional and Herbal Drugs ; (24): 3554-3559, 2017.
Article in Chinese | WPRIM | ID: wpr-852558

ABSTRACT

Objective To explore the protective effects of glycyrrhetic acid derivatives (TY501) on carbon tetrachloride-induced liver fibrosis in mice. Methods The mice liver fibrosis was established by classical CCl4, and TY501 was given in three kinds of dosage (45, 15, and 5 mg/kg), with colchicine serving as control. After 30 d treatment, the liver function, fibrosis and the levels of Hyp and TGF-β1 were detected. Moreover, the histopathological changes were detected by HE and Masson staining. Results Compared with model group, the levels of ALT, AST, ALP, ALB, HA, LN, PCIII, CIV, Hyp, and TGF-β1 were all decreased, with high-dose group being the most significant (P < 0.05, 0.01). Histopathological examination showed that liver fibrosis of those mice treated with TY501 was improved to some extent. Conclusion TY501 can significantly protect carbon tetrachloride-induced hepatic fibrosis.

6.
Journal of International Pharmaceutical Research ; (6): 533-538,542, 2016.
Article in Chinese | WPRIM | ID: wpr-604101

ABSTRACT

Objective To establish a sensitive,simple and accurate HPLC-MS/MS method to quantify glycyrrhetic acid(glyc?yrrhetinic acid)in mice blood,and to further study pharmacokinetic profiles of glycyrrhetic acid after oral administration of glycyrrhi?zin and Bu-Zhong-Yi-Qi-Wan(BY). Methods Rats were intragastric administered of glycyrrhizin(glycyrrhizic acid,61.5 mg/kg) and BY extract(3 g/kg,with the same mole of glycyrrhizin moiety),respectively. Plasma samples were collected after administration and extracted with liquid-liquid extraction,then by separated by liquid chromatography on a C8 reversion phase chromatographic col?umn with gradient elution. Concentration of glycyrrhetic acid was detected by the validated HPLC-MS/MS. Non-compartmental pharma?cokinetic profiles were constructed using the software of Das 2.0 software(Shanghai,China),and the pharmacokinetic parameters were compared using unpaired Student′s t-test. Results This bioanalytical method was fully validated and showed good linearity(r>0.99),wide dynamic range(5-1000 ng/ml),and favorable accuracy and precision. Compared with the glycyrrhizin pure form group, BY significantly reduced the Cmax and AUC0-t of glycyrrhetic acid by 56%and 76%,respectively. Whereas no significant differences in Tmax,T1/2 and MRT were observed between the two groups. Conclusion The constituents in the BY prescription have significantly reduced the oral bioavailability of glycyrrhetic acid in rats than those in the glycyrrhizin pure form and the results indicate that some components in the BY have an inhibition effect on the absorption process of glycyrrhizin in the gut.

7.
Journal of International Pharmaceutical Research ; (6): 533-538, 2016.
Article in Chinese | WPRIM | ID: wpr-845557

ABSTRACT

Objective To establish a sensitive, simple and accurate HPLC-MS/MS method to quantify glycyrrhetic acid(glycyrrhetinic acid)in mice blood, and to further study pharmacokinetic profiles of glycyrrhetic acid after oral administration of glycyrrhizin and Bu- Zhong- Yi- Qi- Wan (BY). Methods Rats were intragastric administered of glycyrrhizin(glycyrrhizic acid, 61.5 mg/kg) and BY extract(3 g/kg, with the same mole of glycyrrhizin moiety), respectively. Plasma samples were collected after administration and extracted with liquid-liquid extraction, then by separated by liquid chromatography on a C8 reversion phase chromatographic column with gradient elution. Concentration of glycyrrhetic acid was detected by the validated HPLC-MS/MS. Non-compartmental pharmacokinetic profiles were constructed using the software of Das 2.0 software(Shanghai, China), and the pharmacokinetic parameters were compared using unpaired Student’s t-test. Results This bioanalytical method was fully validated and showed good linearity(r> 0.99), wide dynamic range(5-1000 ng/ml), and favorable accuracy and precision. Compared with the glycyrrhizin pure form group, BY significantly reduced the Cmax and AUC0-t of glycyrrhetic acid by 56% and 76%, respectively. Whereas no significant differences in Tmax, T1/2 and MRT were observed between the two groups. Conclusion The constituents in the BY prescription have significantly reduced the oral bioavailability of glycyrrhetic acid in rats than those in the glycyrrhizin pure form and the results indicate that some components in the BY have an inhibition effect on the absorption process of glycyrrhizin in the gut.

8.
Chinese Pharmacological Bulletin ; (12): 210-215, 2015.
Article in Chinese | WPRIM | ID: wpr-473693

ABSTRACT

Aim To investigate TY501′s role in bleo-mycin ( BLM )-induced pulmonary fibrosis in rats. Methods Forty rats were randomly divided into 5 groups, including the sham operation, BLM, PFD, TY501(high and low dose) groups. After administra-tion of BLM intratracheally, PFD and TY501 were giv-en in each group daily, according to the dosage de-signed during 21 days. Lung coefficient, PaO2 were tested before killing the rats. The contents of ALB, ALP, LDH, GSH, HYP were detected by regent kit respectively. PCⅢ and COL4 were determined by ELISA. Results ( 1 ) Some indicators of alveolitis in early stage of IPF: the contents of lung coefficient in three treatment groups were lower and PaO2 was higher than those in BLM group ( P<0. 05 ); compared with BLM group, the contents of ALB, ALP, LDH in the treatment groups reduced on 21 st day ( P<0. 05 );the expression of GSH in BLM group was increased for feedback regulation and higher than the treatment groups and the sham operation group (P<0. 05);(2) some indicators of pulmonary interstitial fibrosis in late stage of IPF:the expressions of HYP, PCⅢand COL4 were reduced after the treatment. There were signifi-cant differences compared with BLM group ( P <0. 05 ) . Conclusions TY501 is valuable for the ther-apy of IPF, the same as the positive drug pirfenidone. TY501 attenuates BLM-induced pulmonary fibrosis, which may be related to the affection of TGF-βpathway and inhibition of MMPs.

9.
Chinese Traditional and Herbal Drugs ; (24): 1552-1557, 2013.
Article in Chinese | WPRIM | ID: wpr-855273

ABSTRACT

Objective: To study the chemical constituents from the roots and rhizomes of Glycyrrhiza uralensis. Methods: The compounds were separated and purified by solvent and chromatographic methods. Their structures were identified by spectroscopic techniques. Results: Fourteen triterpenoid saponins isolated from 50% ethanol extract of the roots and rhizomes of G. uralensis were identified as uralsaponin C (1), uralsaponin D (2), licorice-saponin A3 (3), uralsaponin F (4), 22β-acetoxyl-glycyrrizin (5), 24-hydroxyl-licorice-saponin E2 (6), licorice-saponin E2 (7), licorice-saponin G2 (8), 22β-acetoxyl-glyrrhaldehyde (9), 3β-O-[β-D-glucuronopyranosyl-(1→2) - β-D-glucuronopyranosyl]-glycyrretol (10), araboglycyrrhizin (11), licorice-saponin J2 (12), glycyrrhizin (13), and glycyrrhetic acid monoglucuronide (14). Compounds 1-14 showed the cytotoxic activity against the human cancer cell lines MGC-803, SW620, and SMMC-7721 with IC50 > 100 μmol/L. The aglycones of compounds 2, 6-8, and 13 displayed the inhibition on the growth of cancer cells with IC50 at 18.3-41.6 μmol/L. Conclusion: Compound 14 is a new natural product, and compound 11 is isolated from the plant for the first time; Compounds 1-14 show no cytotoxic activity against the human cancer cell lines MGC-803, SW620, and SMMC-7721, and the aglycones of compounds 2, 6-8, and 13 could significantly increase the cytotoxic activity after hydrolysis.

10.
Chinese Herbal Medicines ; (4): 118-125, 2012.
Article in Chinese | WPRIM | ID: wpr-499793

ABSTRACT

Objective To investigate the metabolism of strychnine (STN) and the metabolic interaction between STN and glycyrthetic acid (GA) in vitro.MethodsHuman liver microsomes (HLM) and human recombinant cytochrome P450 (CYP) isoforms were employed to study the metabolism of STN and the metabolic interaction of STN with GA in vitro.ResultsIn HLM,the Km,Vmax,and clearance of STN were 88.50 μmol/L,0.88 nmol/(mg·min),and 9.93 mL/(mg·min),respectively.STN was metabolized mainly by CYP3A4.However,STN noncompetitively inhibited CYP3A4-catalyzed testosterone 6β-hydroxylation with IC50 value of 5.9 μtmol/L and Ki value of 5.5μmol/L.Moreover,GA competitively inhibited STN metabolism with IC5o value of 10.6 μmol/L and Ki value of 17.7 μmol/L.ConclusionAlthough STN is mainly metabolized by CYP3A4 in vitro,STN has noncompetitive inhibition on CYP3A4-catalyzed testosterone 6β-hydroxylation.Moreover,GA could competitively inhibit STN metabolism.The present work is helpful to elucidate the metabolic interaction between STN and GA.

11.
Malaysian Journal of Microbiology ; : 75-82, 2012.
Article in English | WPRIM | ID: wpr-625635

ABSTRACT

Glycyrrhizin (GL), the well-known sweet saponin of licorice, has been used as a food-additive and as a medicine. Its aglycone, glycyrrhetic acid (GA) showed antiinflamatory, antiulcer and antiviral properties. GA is now produced form GL by acid hydrolysis. However, it is difficult to obtain GA in a good yield by using this method, because many by-products are also produced. Screening of different microorganisms (13 bacteria, 2 yeasts and 23 fungi) for production of GA from GL revealed that Aspergillus niger NRRL 595 produced the highest yield of GA. The bioconversion of GL by A. niger NRRL 595 for 96 h, followed by isolation and purification of the transformation products led to the separation of two conversion products, namely: GA and 3-oxo-GA. Confirmation of the identity of these products was established by determination of their Rf values, m.p., and IR, UV, MS and NMR spectra. The conditions for cultivation of this fungus with the maximum hydrolytic activity for the maximum yield of GA were investigated. Based on the results, A. niger NRRL 595 was cultivated with a medium composed of 1.75 % GL, 0.5 % glucose, 0.8 % corn steep liquor at pH 6.5 at 32 °C for 96 h. The cultivation of fungal cells under the latter conditions afforded GA and 3-oxo-GA in a yield of 65 % and 22 %, respectively.

12.
China Pharmacy ; (12)2007.
Article in Chinese | WPRIM | ID: wpr-532951

ABSTRACT

OBJECTIVE:To prepare glycyrrhetic acid derivatives-modified norcantharidin(NC)liposome(GDNL)and study its liver-targeting property.METHODS:Gal-GAOSt targeting molecules were synthesized to modify NC and prepare GDNL,with the parameters such as the entrapment efficiency and particle diameter,etc.investigated.Mice were enrolled to be injected with GDNL and NC water solution,respectively via vena caudalis followed by determination of NC concentration in different tissues to compute the targeting-index(TI)of GDNL in liver.RESULTS:The prepared GDNL had an entrapment efficiency of 56.29%,particle diameter of(210?20)nm and TI of 5.213 in liver.CONCLUSION:The prepared GDNL has high entrapment efficiency and remarkable liver-targeting property.

13.
China Pharmacy ; (12)2005.
Article in Chinese | WPRIM | ID: wpr-528756

ABSTRACT

OBJECTIVE:To determine the content of glycyrrhetic acid in zhenkening capsules by RP-HPLC.METHODS:The separation was performed on Hypersil C 18,the mobile phase consisted of methanol-water-glacial acetic acid(87∶13∶2.5)with flow rate at 1.0ml/min and detection wavelength at 254nm,the column temperature was set at room temperature.RE-SULTS:The calibration cure of glycyrrhetic acide was linear in the concentration range of 10~120?g/ml(r=0.9999),the average recovery was 99.68%(RSD=0.49%).CONCLUSION:This method is simple,fast,accurate,and suitable for the determination of glycyrrhetic acid in zhenkening capsules.

14.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12)2004.
Article in Chinese | WPRIM | ID: wpr-560624

ABSTRACT

AIM: To quantify magnesium isoglycyrrhizinate(MGL) and glycyrrhetic acid in the plasma of dog by develop a simple, rapid, sensitive high-performance liquid chromatography (HPLC-UV) method. METHODS: HPLC-UV methods with wavelength 252 nm were used for the quantitation of MGL and GA in plasma. The concentration of MGL and GA were assayed on a Kromasil ODS-1 C18 column with the column temperature 25 ℃. The mobile phase was a gradient system with 0.1 % diethylamine in water (pH 4.60 ) and acetonitrile at a flow rate of 1.0 ml?min~ -1 . RESULTS: There was a good linear response range of 0.2 -2.5 mg?L~ -1 and 2.5 -100 mg?L~ -1 , while the limit of quantification was 0.2 mg?ml~ -1 . The relative recovery rate of MGL was 94.3 %-101.9 %,GA 96.4 %-101.9 % (n=5);the absolute recovery rate was MGL 78.7 %-87.0 %, GA 77.5 %-87.7 % (n=5). The intra-day and inter-day variations were all less than 15% (n=5). The plasma samples preserved in refrigerator is stable at -20 ℃ for 14 days, freeze thawing 3 times and at room temperature for 10 h without degradation. CONCLUSION: This method is shown to be specific, sensitive, reliable and suitable for the quantitative determination of magnesium isoglycyrrhizinate following oral administration in biological sample.

15.
Journal of Medical Postgraduates ; (12)2003.
Article in Chinese | WPRIM | ID: wpr-595577

ABSTRACT

Objective:The 11?-hydroxysteroid dehydrogenase(11?-HSD) plays an important role in tumor biological behavior,and the 11?-HSD inhibitor Glycyrrhetinic acid(GA) may have an anticancer effect,although its mechanism remains unkown.This study aimed to observe the expressions of 11?-HSD 1 and 2 in colorectal cancer and the effects of glucocorticoid and GA on colorectal cancer cells.Methods: The mRNA expressions of 11?-HSD1 and 2 in the human colorectal cancer cell line HCT-8 were detected by reverse transcription polymerase chainreaction(RT-PCR),and the protein expressions of 11?-HSD1 and 2 were detected by Western blot.The inhibition of the growth of the HCT-8 cells was determined by MTT assay after treated with glucocorticoid,cosubstrate,GA only or their combination.Results: The expression of 11?-HSD2 mRNA and proteins but not that of 11?-HSD1 mRNA and proteins was expressed in the HCT-8 cells.The rate of cell growth inhibition was(40.87 ? 1.47)% after a 12-hour treatment with cortisol,and it was(5.79 ? 0.20)% in the cortisol + NAD group,with statistically significant difference(P

16.
Chinese Traditional and Herbal Drugs ; (24)1994.
Article in Chinese | WPRIM | ID: wpr-681895

ABSTRACT

Object To establish the process of supercritical CO 2 extraction of glycyrrhetic acid from Glycyrrhiza uralensis Fisch.. Methods The comparison methods among supercritical CO 2 extraction, Soxhleth extraction and ultrasonic extraction were conducted. Results The optimized supercritical CO 2 extraction conditions were 30 MPa, pressure; 70 meshes, granularity of material; 80% ethanol, modifying agent; 45 ℃, extraction temperature; 2 hours, extraction time. Conclusion The results show that supercritical CO 2 extraction has an advantage over any other extractions of glycyrrhetic acid from G. uralensis.

17.
Chinese Traditional Patent Medicine ; (12)1992.
Article in Chinese | WPRIM | ID: wpr-683588

ABSTRACT

AIM: To compare the contents of baicalin,paeoniflorin and glycyrrhetic acid in the seperated and mixed decoction of Huangqin Decoction(Radix Scutellariae,Radix Paeoniae alba,Radix et Rhizoma Glycyrrhizae and Fructus Jujubae). METHODS: The contents of baicalin,paeoniflorin and glycyrrhetic acid were analyzed by HPLC.Chromatographic conditions included: Hypersil BDS C_(18) column and the mobile phase consisted of a mixture of methanol-water-phosphoric acid(47(∶)53(∶)0.2),acetonitrile-water-phosphoric acid(18(∶)82(∶)0.1) and methanol-water-phosphate buffer solution(70(∶)29(∶)1).Baicalin,paeoniflorin and glycyrrhetic acid were detected at 280 nm,230 nm and 250 nm respectively. RESULTS: The linear range of baicalin,paeoniflorin and glycyrrhetic acid were 2.88—72.00 ?g/mL,2.85—22.80 ?g/mL and 4.16—52.00 ?g/mL respectively.The contents of baicalin in the mixed decoction was higher than that in the seperated decoction.The contents of paeoniflorin and glycyrrhetic acid in the mixed decoction were almost as same as that in seperated decoction. CONCLUSION: The contents of active ingredients in the mixed and seperated decoction are different.

18.
Chinese Pharmacological Bulletin ; (12)1987.
Article in Chinese | WPRIM | ID: wpr-553598

ABSTRACT

AIM To analyze the effects of glycyrrhetic acid (GA) on c-fos expression and cell proliferation in rat vascular smooth muscle cell (VSMC), and to figure out the mechanisms of binding GA to angiotensin Ⅱ(AⅡ) receptor. METHODS Primary cell culture of rat VSMC, Northern blot, TdR incorporation DNA assay and MTT assay were used in this study. RESULTS ① GA at both low (1?10 -9 mol?L -1) and high concentration (1?10 -5 mol?L -1) quickly induced c-fos expression in VSMC. Sar-AⅡ(1?10 -5 mol?L -1)inhibited both GA induced and AⅡ (1?10 -5 mol?L -1) induced c-fos expression. GA enhanced AⅡ induced c-fos expression at both low and high concentration in VSMC. ② Low level of GA stimulated the proliferation of VSMC. This stimulatory effect decreased with increasing GA concentration, and changed to be inhibitory at high concentration of GA. Not only did Sar-AⅡ eliminate the stimulatory effect of low concentration of GA on cell proliferation, it also eliminated the inhibitory effect of high concentration of GA. Low concentration of GA enhanced the stimulation of AⅡon cell proliferation, while the inhibitory effect of high concentration of GA on cell proliferation was relieved by adding 1?10 -7 mol?L -1 AⅡ. CONCLUSION This study suggests that GA activates transcription factor c-fos and promotes the proliferation of VSMC. GA may exert its effects on cells through AT 1 receptor since it induces similar changes as AⅡ and its effects can be inhibited by AT 1 receptor antagonist.

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