1.Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats.
Kyubok JIN ; Tae Hee KIM ; Yeong Hoon KIM ; Yang Wook KIM
The Korean Journal of Internal Medicine 2013;28(2):197-205
BACKGROUND/AIMS: Magnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats. METHODS: Fifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks. RESULTS: Systolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats. CONCLUSIONS: Concurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.
Aldosterone/blood
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Angiotensin II/blood
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Angiotensin II Type 1 Receptor Blockers/*pharmacology
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Animals
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Antihypertensive Agents/*pharmacology
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Biological Markers/blood
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Blood Pressure/*drug effects
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*Dietary Supplements
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Disease Models, Animal
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Hypertension/blood/*drug therapy/pathology/physiopathology
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Kidney/drug effects/pathology
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Magnesium/blood/*pharmacology
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Magnesium Deficiency/blood/*drug therapy/pathology/physiopathology
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Male
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Rats
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Rats, Sprague-Dawley
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Systole
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Time Factors
2.Catestatin could ameliorate proliferating changes of target organs in spontaneously hypertensive rats.
Ran LIU ; Ning-ling SUN ; Song-na YANG ; Jian-qiang GUO
Chinese Medical Journal 2013;126(11):2157-2162
BACKGROUNDCatestatin, a chromogranin A-derived peptide, is a potent antagonist of nicotine-evoked catecholamine release. We know that catecholamine plays an important role in cardiovascular remodeling induced by hypertension, therefore we hypothesized that catestatin would affect target-organ structure during hypertension.
METHODSTwelve spontaneously hypertensive rats (SHRs) were randomized to SHR control group and catestatin group, the normal control group was comprised of six healthy Wistar-Kyoto rats of the same age. Tail-cuff blood pressure and pulse rate were obtained at weeks 1, 4 and 8. At the end of the eight-week period, the heart, abdominal aorta and left kidney were excised and weighed, VG staining was done and the intima-media thickness of vessels and the collagen volume fraction were assessed by an image acquisition and analysis system. The proliferating cell nuclear antigen (PCNA) was observed by immunohistochemistry, and real time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of proliferative genes including cyclin A, ki67 and PCNA in the abdominal aorta.
RESULTSAll the parameters in SHR observed in the present study increased significantly compared to Wistar Kyoto rats (P < 0.01). With intervention with catestatin, the systolic blood pressure decreased slightly but it was not significantly different from the SHR control, the cardiac mass index and left ventricular mass index both decreased significant ly, the collagen volume fraction decreased by nearly 30% in the heart, by 25% in vessels and by 10% in the kidney, and the intima-media thickness and expression of proliferative genes, including cyclin A, ki67 and PCNA, in the abdominal aorta also decreased significant ly.
CONCLUSIONSThe present study indicated that catestatin could ameliorate proliferating changes of heart, kidney and vessels during hypertension, especially to the deposition of interstitial collagen. Blood pressure was not the main factor to mediate this effect, which suggested that catestatin could become a novel protective factor for hypertensive target organs.
Animals ; Aorta, Abdominal ; drug effects ; pathology ; Blood Pressure ; Cell Proliferation ; drug effects ; Chromogranin A ; pharmacology ; Heart Rate ; drug effects ; Hypertension ; drug therapy ; pathology ; physiopathology ; Kidney ; drug effects ; pathology ; Male ; Peptide Fragments ; pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY
3.Effect of traditional and integrative regimens on quality of life and early renal impairment in elderly patients with isolated systolic hypertension.
Hao LI ; Long-tao LIU ; Wen-ming ZHAO ; Jian-gang LIU ; Ming-jiang YAO ; Yong-xiang HAN ; Yan-peng SHEN ; Xing-dong LIU ; Li LIU ; Xue-mei WANG ; Lin-lin CAI ; Jie GUAN
Chinese journal of integrative medicine 2010;16(3):216-221
OBJECTIVETo observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH).
METHODSA multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment.
RESULTSAfter treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05).
CONCLUSIONSChinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.
Aged ; Aged, 80 and over ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Integrative Medicine ; Kidney ; drug effects ; pathology ; physiopathology ; Male ; Quality of Life ; Systole ; drug effects ; physiology
4.Clinical observation on treatment of hypertension (yin-deficiency with sthenic-yang syndrome type) with Zhongfu Hypotension Capsule.
Qiu-ai KOU ; Hua-ping YU ; Guo-dong ZHOU
Chinese Journal of Integrated Traditional and Western Medicine 2007;27(8):745-748
OBJECTIVETo observe the efficacy and safety of zhongfu hypotension capsule (ZHC) in treating hypertension of yin-deficiency with sthenic-yang syndrome type.
METHODSAdopting the stratified, block randomized, double-blinded, double-dummy, positive parallel controlled, multi-centered clinical trial method, the tested group was treated by orally taken 3 capsules of ZHC (0.5 g/capsule) twice a day, and the control group was treated by orally taken Lotensin Tablet 1 tablet (10 mg/tab.) once a day. And all received the adiaphorous drug with the dosage-form mimic to that used in the tested group. The therapeutic course was 4 weeks for both groups.
RESULTSThe markedly effective rate and the total effective rate in reducing blood pressure was 58.65% and 79.81% respectively in the tested group, and 60.51% and 78.34% respectively in the control group; while the markedly effective rate and the total effective rate for alleviating TCM syndrome was 21.15% and 78.85% in the tested group, and 25.48% and 86.62% in the control group respectively. Comparisons between the two groups showed insignificant difference (P > 0.05).
CONCLUSIONZHC has good efficacy and is safety in treating hypertension.
Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzazepines ; therapeutic use ; Blood Pressure ; drug effects ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Middle Aged ; Phytotherapy ; Syndrome ; Tablets ; Yin Deficiency ; drug therapy ; pathology
5.Effect of different doses of losartan on cirrhotic portal hypertensive colopathy in rats.
Li-Juan HUO ; Xiao-Dong HAN ; Ling-Lin TIAN
Chinese Journal of Hepatology 2010;18(1):69-70
Animals
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Colon
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blood supply
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pathology
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Colonic Diseases
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drug therapy
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etiology
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physiopathology
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Hemodynamics
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Hepatic Veins
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pathology
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physiopathology
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Hypertension, Portal
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complications
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physiopathology
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Intestinal Mucosa
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blood supply
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drug effects
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pathology
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Liver Cirrhosis, Experimental
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complications
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Losartan
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administration & dosage
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therapeutic use
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Male
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Microscopy
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Portal Pressure
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drug effects
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Random Allocation
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Rats
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Rats, Wistar
6.Effects of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein in hypertensive patients with mild LDL-C elevation.
Ze-peng LIN ; Zhi-wei ZHANG ; Rong-kui ZHANG ; Ping-chun SHU ; Shi-qin WU
Journal of Southern Medical University 2010;30(3):588-590
OBJECTIVETo observe the effect of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein (hs-CRP) in hypertensive patients with mild elevation of LDL-C.
METHODSSeventy-nine patients with a SBP of 140-179 mmHg and/or a DBP of 90-109 mmHg and mild elevated LDL-C were treated with rosuvastatin for 12 months (n=40) or not (n=39). The changes of hs-CRP, arteriosclerosis plaque and cardiac function at the end of the 12-months treatment relative to the baseline levels were analyzed.
RESULTSAfter 12 months of treatment, LDL-C was decreased by 33.2% in rosuvastatin group but remained unchanged in patients without rosuvastatin treatment. The left ventricular peak filling rate (LVPFR) increased significantly from 1.85 to 2.59 (P<0.05) and the serum levels of hs-CRP reduced significantly (P<0.05) after rosuvastatin treatment. The size of the plaques reduced significantly after a 12-month rosuvastatin therapy.
CONCLUSIONRosuvastatin therapy on the basis of conventional anti-hypertensive drugs can obviously improve the left ventricular diastolic function and produce favorable effects on arteriosclerotic plaques.
Aged ; Arteriosclerosis ; complications ; pathology ; C-Reactive Protein ; metabolism ; Cholesterol, LDL ; blood ; Female ; Fluorobenzenes ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hyperlipidemias ; drug therapy ; pathology ; physiopathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; therapeutic use ; Ventricular Function, Left ; drug effects
7.Protective effects of Sapindus saponins in spontaneously hypertensive rats.
Ming CHEN ; Zhi-Wu CHEN ; Zi-Jiang LONG ; Ju-Tao WANG ; Ya-Juan WANG ; Jin-Lin LIU
Chinese journal of integrative medicine 2015;21(1):36-42
OBJECTIVESTo investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms.
METHODSThirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups (8 in each group): model group (placebo), positive control group (27 mg/kg of Captopril Tablets), Sapindus saponins groups (27 mg/kg and 108 mg/kg, respectively). Another 8 healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter (BP-6). Furthermore, the contents of angiotensin II (Ang II) in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA), the gene expression of receptor angiotensin type 1 (AT1R) in aorta was determined by quantitative realtime polymerase chain reaction (qRT-PCR). The protein expression of transforming growth factor-β1 (TGF-β1) and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) was determined by Western blotting. The contents of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin (HE) or Masson staining.
RESULTSThirty minutes after single or continuous treatment, systolic blood pressure (SBP) was reduced significantly in Sapindus saponins groups. And the contents of AngII, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF-β1 were significantly suppressed dose-dependently (P<0.05 or P<0.01). With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly.
CONCLUSIONSOur findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang II and AT1R.
Angiotensin II ; metabolism ; Animals ; Aorta ; drug effects ; pathology ; physiopathology ; Blood Pressure ; drug effects ; Collagen ; metabolism ; Female ; Hypertension ; blood ; drug therapy ; enzymology ; physiopathology ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Phosphorylation ; drug effects ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Inbred SHR ; Receptor, Angiotensin, Type 1 ; metabolism ; Renin-Angiotensin System ; drug effects ; Sapindus ; chemistry ; Saponins ; pharmacology ; therapeutic use ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; p38 Mitogen-Activated Protein Kinases ; metabolism
8.Effects of Xuezhikang and pravastatin on circulating endothelial progenitor cells in patients with essential hypertension.
Li LU ; Jian-zhong ZHOU ; Li WANG ; Tie-xu ZHANG
Chinese journal of integrative medicine 2009;15(4):266-271
OBJECTIVETo investigate the impacts of Xuezhikang (XZK) or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells (CEPCs) in essential hypertensive (EH) patients.
METHODSEighty-eight EH patients were enrolled into the study and randomly assigned to the antihypertensive drug treatment group (ATH group, 29 cases), the pravastatin treatment group (PRA group, 29 cases) and the Xuezhikang treatment group (XZK group, 30 cases). Patients in the 3 groups were treated with routine antihypertensive drugs. In addition, pravastatin and Xuezhikang were given to the patients in the PRA group and XZK group, respectively. After an eight-week treatment, CEPCs were counted using a laser scanning confocal microscope, and their proliferation function was evaluated by the MTT colorimetric assay and the adherent cell number was counted to estimate the adhesion function.
RESULTSAfter the treatment, CEPCs in the PRA group (116.60+/-5.70) and XZK group (114.40+/-6.55) was significantly higher than that in the ATH group (88.00+/-6.32, P<0.01). CEPCs proliferation capability and the adhesion function in the PRA group (0.406+/-0.016, 33.60+/-4.26) and XZK group (0.415+/-0.018, 34.30+/-3.77) were obviously superior to those in the ATH group (0.333+/-0.021, P<0.01; 23.30+/-3.19, P<0.01). No significant difference was found between the pravastatin group and the XZK group.
CONCLUSIONSCombined use of XZK or pravastatin with the anti-hypertensive therapy could increase the CEPCs number and improve their function in EH patients with the blood pressure controlled by antihypertensive drugs, leading to benefits independent of pressure-lowering effects.
Aged ; Anticholesteremic Agents ; administration & dosage ; Antidiuretic Agents ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Blood Cell Count ; Calcium Channel Blockers ; administration & dosage ; Cell Adhesion ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Endothelial Cells ; drug effects ; pathology ; physiology ; Female ; Humans ; Hypertension ; blood ; drug therapy ; pathology ; physiopathology ; Integrative Medicine ; methods ; Male ; Middle Aged ; Pravastatin ; administration & dosage ; Stem Cells ; drug effects ; pathology ; physiology
9.High-Dose Terazosin Therapy (5mg) in Korean Patients with Lower Urinary Tract Symptoms with or without Concomitant Hypertension: A Prospective, Open-Label Study.
Cheol KWAK ; Jeong Ki LEE ; Ja Hyeon KU
Yonsei Medical Journal 2007;48(6):994-1000
PURPOSE: We determined the efficacy and safety of a relatively high dose of terazosin (5mg) in Korean patients with lower urinary tract symptoms (LUTS), with or without concomitant hypertension. MATERIALS AND METHODS: From July to December 2006, 200 men who consecutively presented with LUTS were prospectively studied. Eight weeks after treatment, blood pressure (BP), uroflowmetry, and International Prostate Symptom Score (I-PSS) were assessed. For analysis purposes, patients were stratified according to concomitant hypertension. Of the 200 patients, 173 completed the scheduled eight-week treatment period. RESULTS: At baseline, no differences were evident in the two groups in terms of I-PSS, Qmax, PVR and BP. After eight weeks of treatment-although I-PSS and uroflowmetry parameters were not significantly different in the two groups-systolic and diastolic BP in the non-hypertensive control group were higher than in the hypertensive group (p= 0.001 and p=0.0100, respectively). Changes in I-PSS, uroflowmetry parameters, and BPs measured at week eight post- treatment commencement did not significantly differ between the two groups. Moreover, the addition of 5mg of terazosin to antihypertensives did not cause a significant reduction in either systolic or diastolic BP in either group. CONCLUSION: Adding terazosin to existing antihypertensive regimens did not seem to increase the incidence of adverse events. Our findings suggest that 5mg terazosin is effective and that it has an acceptable safety profile as an add-on therapy for patients with LUTS and concomitant hypertension.
Adrenergic alpha-Antagonists/adverse effects/therapeutic use
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Aged
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Asian Continental Ancestry Group
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Blood Pressure/drug effects
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Humans
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Hypertension/complications/*drug therapy/physiopathology
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Korea
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Male
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Middle Aged
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Prazosin/adverse effects/*analogs & derivatives/therapeutic use
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Prospective Studies
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Prostate/drug effects/pathology
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Treatment Outcome
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Urodynamics/drug effects
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Urologic Diseases/complications/*drug therapy/ethnology
10.Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats.
Li-li ZHAO ; Hong-juan CHEN ; Jun-zhu CHEN ; Min YU ; Yun-lan NI ; Wei-fang ZHANG
Journal of Zhejiang University. Science. B 2008;9(6):448-454
OBJECTIVETo assess the effect of angiotensin II type 1 (AT(1)) receptor antagonist losartan on myocardium connexin43 (Cx43) gap junction (GJ) expression in spontaneously hypertensive rats (SHRs) and investigate possible mechanisms.
METHODSSixteen 9-week-old male SHRs and 8 age-matched male Wistar-Kyoto (WKY) rats were included in this study. SHRs were randomly divided into two groups to receive losartan at 30 mg/(kg x d) by oral gavage once daily for 8 weeks (SHR-L) or vehicle (0.9% saline) to act as controls (SHR-V); WKY rats receiving vehicle for 8 weeks served as normotensive controls. At the end of the experiment, rats were sacrificed and the hearts were removed. Expressions of Cx43 and nuclear factor-kappaB p65 (NF-kappaB p65) proteins in all three groups were observed and further investigations on the effect of angiotensin II type 1 receptor antagonist losartan (30 mg/(kg x d), 8 weeks) on Cx43 expression were conducted with Western blot and immunohistochemistry. NF-kappaB p65 protein in nuclear extracts was determined by Western blot.
RESULTSLeft ventricular (LV) hypertrophy was prominent in SHRs, Cx43 and NF-kappaB p65 protein expressions were obviously upregulated and Cx43 distribution was dispersed over the cell surface. Treatment with losarton reduced the over-expressions of Cx43 and NF-kappaB p65 in LV myocardium. The distribution of Cx43 gap junction also became much regular and confined to intercalated disk after losartan treatment.
CONCLUSIONCx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin II type 1 receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-kappaB pathway.
Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Blotting, Western ; Connexin 43 ; metabolism ; Hypertension ; drug therapy ; metabolism ; physiopathology ; Hypertrophy, Left Ventricular ; drug therapy ; metabolism ; pathology ; Losartan ; pharmacology ; Male ; Myocardium ; metabolism ; Natriuretic Peptide, Brain ; blood ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Transcription Factor RelA ; metabolism