Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) o...Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) or a continuous subcutaneous infusion of a Miso extract attenuates hypertension in Dahl S rats. Materials and Methods: We investigated the effects of a bolus, i.p. injection of 50 mg Miso extract in 0.5 mL on hypertension in Dahl S rats, and examined whether a long-term subcutaneous infusion of the Miso extract (50 mg Miso/day), using an osmotic mini-pump working for 14 days, attenuates hypertension in Dahl S rats. Results: A bolus, i.p. injection of 50 mg Miso extract decreased SBP in 2 hrs. The reduction was significant at 4 hrs, and SBP returned to the baseline at 24 hrs. The SBP reduction at 4 hrs after the injection was increasingly greater each day during the 4 days. The SBP reduction by the Miso extract was dose-dependent and the antihy-pertensive activity occurs in a <5 kDa fraction of the extract. The subcutaneous infusion of 50 mg Miso extract/day for 14 days significantly attenuated hypertension in Dahl S rats. The SBP reduction was associated with significant decreases in the heart and kidney weights. Urinary protein excretion significantly decreased in the Miso group. The SBP reduction was not associated with increases in either urinary sodium excretion or fractional excretion of sodium. Conclusions: SBP reduction by very low-dose of the Miso extract may be mediated partly by mechanisms other than renal sodium handling.展开更多
Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast mi...Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.展开更多
BACKGROUND: High incidence of stroke at interchange period of autumn and winter was demonstrated by epidemiological survey, and the specific causes should be further investigated. OBJECTIVE: To investigate the influ...BACKGROUND: High incidence of stroke at interchange period of autumn and winter was demonstrated by epidemiological survey, and the specific causes should be further investigated. OBJECTIVE: To investigate the influence of artificial cold exposure on the incidence of stroke in renovascular hypertensive rats (RHR), and analyze the association with blood pressure and cold-inducible RNA binding protein (CIRP) mRNA expression in brain tissue. DESIGN: A completely randomized grouping design, a randomized control animal trial. SETTINGS: Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University; Department of Chemistry, Open laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong. MATERIALS: Male SD rats (n=460), weighing 80 - 100 g were obtained from Guangdong Province Health Animal Unit. A modified RXZ-300A intelligent artificial climate cabinet (Ningbo Jiangnan Instrument Co. ,Ltd., China). METHODS: The experiment were processed in the Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University and the Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong from October 2004 to November 2005. Rats (n = 400) were operated to establish 2-kidney 2-clip RHR model as described previously. The sham-operated rats (n =60) served as normotensive controls. Eight weeks later, 300 of RHR were randomly selected according to their systolic blood pressure (SBP) and divided into 3 sub-groups (n =100 per group): mild hypertensive group (SBP of 160 - 200 mm Hg), moderate hypertensive group (SBP of 200 - 220 mm Hg) and severe hypertensive group (SBP 〉 220 mm Hg). Each group was further divided into two groups (n =50) under ACE and non-ACE. Normal sham-operated SD rats (n =60), SBP 〈 140 mm Hg, were randomly divided into two groups: Sham-operated control group (n =30) under ACE and non-ACE. To establish the ACE and non-ACE treatment, rats were housed individually in artificial climate cabinet, and ACE was designed as three cycles of 12-hour light of 22℃ (7 : 00 - 19 : 00) and 12-hour dark of 4℃(19 : 00 - 7 : 00). The non-ACE group was kept at 22℃ throughout the experiment. MAIN OUTCOME MEASURES: Blood Pressure changes were measured and stroke symptom were observed; Expression of the CIRP were examined by reverse transcription-polymerase chain reaction. RESULTS: Finally 360 rats were involved in the analysis of results. ①Incidence of stroke: The incidence of stroke in 2k2c RHR was significantly higher after a three-day intermittent (12-hour) ACE (29.3%) as compared with that in non-ACE (17.3%) (P 〈 0.05). Furthermore, the severe hypertensive 2k2c RHR (BP 〉 220 mm Hg) was found to have much higher incidence of stroke (66%, 33/50) than the mild (8%, 4/50) and moderate (18%) hypertensive 2k2c RHR. ②CIRP mRNA in brain tissue: ACE treatment stimulated the mRNA expression of CIRP in non-stroke 2k2c RHR but not in stroke 2k2c RHR (P 〈 0.05). CONCLUSION: High blood pressure and low expression of CIRP are associated with ACE induced stroke.展开更多
AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was r...AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.展开更多
Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor p...Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normal tension was 11. 9±8. 2ml/ min/100g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin Ⅱthan 0.5mg/ ml methoxamine, however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an Increase seen in the tumor. A pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrin and ethylphenylephrine. In addition, metaraminol and phenyleprine as well as 1. 0 and 2. 5mg/ ml methoxamine were not found to significantly change blood flow of the tumor.展开更多
文摘Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) or a continuous subcutaneous infusion of a Miso extract attenuates hypertension in Dahl S rats. Materials and Methods: We investigated the effects of a bolus, i.p. injection of 50 mg Miso extract in 0.5 mL on hypertension in Dahl S rats, and examined whether a long-term subcutaneous infusion of the Miso extract (50 mg Miso/day), using an osmotic mini-pump working for 14 days, attenuates hypertension in Dahl S rats. Results: A bolus, i.p. injection of 50 mg Miso extract decreased SBP in 2 hrs. The reduction was significant at 4 hrs, and SBP returned to the baseline at 24 hrs. The SBP reduction at 4 hrs after the injection was increasingly greater each day during the 4 days. The SBP reduction by the Miso extract was dose-dependent and the antihy-pertensive activity occurs in a <5 kDa fraction of the extract. The subcutaneous infusion of 50 mg Miso extract/day for 14 days significantly attenuated hypertension in Dahl S rats. The SBP reduction was associated with significant decreases in the heart and kidney weights. Urinary protein excretion significantly decreased in the Miso group. The SBP reduction was not associated with increases in either urinary sodium excretion or fractional excretion of sodium. Conclusions: SBP reduction by very low-dose of the Miso extract may be mediated partly by mechanisms other than renal sodium handling.
文摘Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.
基金the National Natural Science Foundation of China, No. 30471917the Hong Kong Research Grant Council,No. HKU 7198/01
文摘BACKGROUND: High incidence of stroke at interchange period of autumn and winter was demonstrated by epidemiological survey, and the specific causes should be further investigated. OBJECTIVE: To investigate the influence of artificial cold exposure on the incidence of stroke in renovascular hypertensive rats (RHR), and analyze the association with blood pressure and cold-inducible RNA binding protein (CIRP) mRNA expression in brain tissue. DESIGN: A completely randomized grouping design, a randomized control animal trial. SETTINGS: Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University; Department of Chemistry, Open laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong. MATERIALS: Male SD rats (n=460), weighing 80 - 100 g were obtained from Guangdong Province Health Animal Unit. A modified RXZ-300A intelligent artificial climate cabinet (Ningbo Jiangnan Instrument Co. ,Ltd., China). METHODS: The experiment were processed in the Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University and the Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong from October 2004 to November 2005. Rats (n = 400) were operated to establish 2-kidney 2-clip RHR model as described previously. The sham-operated rats (n =60) served as normotensive controls. Eight weeks later, 300 of RHR were randomly selected according to their systolic blood pressure (SBP) and divided into 3 sub-groups (n =100 per group): mild hypertensive group (SBP of 160 - 200 mm Hg), moderate hypertensive group (SBP of 200 - 220 mm Hg) and severe hypertensive group (SBP 〉 220 mm Hg). Each group was further divided into two groups (n =50) under ACE and non-ACE. Normal sham-operated SD rats (n =60), SBP 〈 140 mm Hg, were randomly divided into two groups: Sham-operated control group (n =30) under ACE and non-ACE. To establish the ACE and non-ACE treatment, rats were housed individually in artificial climate cabinet, and ACE was designed as three cycles of 12-hour light of 22℃ (7 : 00 - 19 : 00) and 12-hour dark of 4℃(19 : 00 - 7 : 00). The non-ACE group was kept at 22℃ throughout the experiment. MAIN OUTCOME MEASURES: Blood Pressure changes were measured and stroke symptom were observed; Expression of the CIRP were examined by reverse transcription-polymerase chain reaction. RESULTS: Finally 360 rats were involved in the analysis of results. ①Incidence of stroke: The incidence of stroke in 2k2c RHR was significantly higher after a three-day intermittent (12-hour) ACE (29.3%) as compared with that in non-ACE (17.3%) (P 〈 0.05). Furthermore, the severe hypertensive 2k2c RHR (BP 〉 220 mm Hg) was found to have much higher incidence of stroke (66%, 33/50) than the mild (8%, 4/50) and moderate (18%) hypertensive 2k2c RHR. ②CIRP mRNA in brain tissue: ACE treatment stimulated the mRNA expression of CIRP in non-stroke 2k2c RHR but not in stroke 2k2c RHR (P 〈 0.05). CONCLUSION: High blood pressure and low expression of CIRP are associated with ACE induced stroke.
基金Supported by The National Natural Science Foundation of China,No.30873464the Research Foundation from Ministry of Education of China,No.108019the Natural Science Foundation of Beijing,China,No.7132150
文摘AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.
文摘Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normal tension was 11. 9±8. 2ml/ min/100g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin Ⅱthan 0.5mg/ ml methoxamine, however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an Increase seen in the tumor. A pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrin and ethylphenylephrine. In addition, metaraminol and phenyleprine as well as 1. 0 and 2. 5mg/ ml methoxamine were not found to significantly change blood flow of the tumor.