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

OBJECTIVETo observe the effects of interleukin-8 monoclonal antibody on smooth muscle cell proliferation and balloon inflation-induced abdominal aorta stenosis in rabbits.

METHODSThirty-six New Zealand white rabbits were randomly assigned to balloon inflation group (group A, n = 12), interleukin-8 monoclonal antibody pre-treated rabbits (2 mg/kg for 3 days before balloon inflation, group B, n = 12) and sham-operated control group (group C, n = 12). Peripheral blood was collected before experiment and at 4 h, 1, 3, 7, 14, and 28 days post balloon inflation or sham operation and the levels of IL-8 were measured by enzyme linked immunosorbent assay (ELISA). The ratio of positive and negative masculine cells in the high power microscopic field was determined in proliferating cell nuclear antigen (PCNA) stained slide. Histopathologic examination was performed in abdominal aorta and luminal area, intima and tunica media area were measured.

RESULTSPlasma interleukin-8 began to rise at 4 h and peaked at 1 day and remained increased up to 28 days after balloon inflation in rabbits of group A, plasma interleukin-8 level in group A was significantly higher than in group B and C at 4 h and thereafter post operation. The ratio of positive and negative masculine cells was significantly increased in group A compared to group C and was significantly lower in group B than in group A. Abdominal aorta stenosis, luminal area, intima and tunica media area were significantly reduced in group B than in group A. Correlation analysis indicated that there were positive relations between plasma IL-8 level and intima thickness, area of intima and tunica media, respectively (r = 0.894, 0.783, 0.801, 0.912, all P < 0.01).

CONCLUSIONSPlasma IL-8 level is increased in this abdominal aorta stenosis model and is positively correlated to the severity of abdominal aorta stenosis. IL-8 monoclonal antibody could significantly reduce abdominal aorta stenosis in this abdominal aorta stenosis model.

Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Aorta, Abdominal ; pathology ; Aortic Coarctation ; drug therapy ; pathology ; Cell Proliferation ; drug effects ; Interleukin-8 ; immunology ; Muscle, Smooth, Vascular ; cytology ; drug effects ; Myocytes, Smooth Muscle ; drug effects ; Rabbits

OBJECTIVETo investigate the autoimmune injuries of diabetic macrovascular disease (aorta) and the protective effects of immunosuppressive agent (cyclosporine A, CsA) on aortic injuries in streptozotocin (STZ)-induced diabetic rats.

METHODSSTZ-induced diabetic rats were assigned randomly to 6 groups which received low (BML or AML, 1 mgxkg(-1)xd(-1)), middle (BMM or AMM, 4 mgxkg(-1)xd(-1)) or high (BMH or AMH, 8 mgxkg(-1)xd(-1)) dose of CsA from 1 week before or after STZ for 8 weeks. Diabetic rats without any treatment, insulin-treated diabetic rats and normal rats were also monitored simultaneously and served as control groups. The pathologic abnormalities of the aorta were verified by HE, Masson staining and electronmicroscopy. The depositions of immunoglobulins (IgG, IgM and IgA) were determined by immunohistochemistry and immunofluorescence methods.

RESULTSAt the end of study, lymphocytes infiltration and collagen content (26 582 +/- 6901) were significantly higher in diabetic aorta than those in non-diabetic aorta (Collagen: 7482 +/- 3491, P < 0.01). The deposited IgG and IgA were also significantly increased in diabetic aorta compared with non-diabetic aorta (IgG: 11 789 +/- 2491 vs. 2518 +/- 1066, P < 0.01; IgA: 17 430 +/- 3159 vs. 1135 +/- 758, P < 0.01). These changes were not affected by insulin while CsA intervention significantly reduced aortic collagen content (BMH: 13 518 +/- 5440, P < 0.01 vs. STZ) and immunoglobulin deposition (BMH: IgG: 7584 +/- 4462; IgA: 6176 +/- 1900, all P < 0.01 vs. STZ). These immunoglobulin deposition changes were confirmed by results of immunofluorescence. Aortic collagen accumulation was positively correlated to aortic immunoglobulin deposition (IgG, r = 0.556, P < 0.01; IgA, r = 0.661, P < 0.01).

CONCLUSIONSOur data suggest that the autoimmune injuries might be a promoting factor in the pathogenesis of the diabetic macrovascular disease which could lead to the development of macrovascular disease. Immunosuppressive agent, such as CsA, could inhibit the abnormal deposition of immunoglobulins and therefore, delay the development of diabetic macrovascular disease in this model.

Animals ; Aorta ; immunology ; pathology ; Aortic Diseases ; etiology ; Cyclosporine ; pharmacology ; Diabetes Mellitus, Experimental ; immunology ; pathology ; Endothelium, Vascular ; drug effects ; pathology ; Immunosuppressive Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

Retinoic acids may inhibit vascular smooth muscle cell proliferation, but may promote endothelial cell proliferation in cell culture. However, little data are available about the effects of all-trans-retinoic acid (ATRA) on endothelial regeneration and functional recovery in an experimental model of vascular injury. Accordingly, we investigated whether ATRA may attenuate neointima formation and accelerate endothelial regeneration with functional recovery in balloon-injured rat aorta. Twelve-week-old male Sprague-Dawley rats underwent endothelial denudation of the thoracic aorta by balloon injury. Fourteen rats were fed a standard rat pellet diet. Another 14 rats were fed ATRA (1.5 mg/day) for 2 weeks. The animals were killed on day 14 for organ chamber study and morphometric analysis. Rats in the ATRA group had a significantly improved acetylcholine-induced relaxation response than those in control group. However, endothelial independent response was not significantly different between the two groups. The extent of reendothelialization was markedly superior in the ATRA group compared with control group (p>0.05). Furthermore, neointima area and the ratio of neointima to medial area were significantly less in ATRA group than in control group (p>0.05). In conclusion, ATRA may accelerate endothelial regeneration with functional recovery, and attenuate neointima formation in balloon-injured rat aorta.
Acetylcholine/pharmacology ; Animal ; Aorta, Thoracic/physiology ; Aorta, Thoracic/injuries ; Aorta, Thoracic/drug effects* ; Balloon Dilatation/adverse effects ; Endothelium, Vascular/physiology ; Endothelium, Vascular/drug effects ; Male ; Muscle Relaxation/physiology ; Muscle Relaxation/drug effects ; Muscle, Smooth, Vascular/physiology ; Muscle, Smooth, Vascular/drug effects ; Rats ; Rats, Sprague-Dawley ; Regeneration/physiology ; Regeneration/drug effects ; Tretinoin/pharmacology* ; Tunica Intima/physiology ; Tunica Intima/pathology* ; Tunica Intima/drug effects* ; Vasodilator Agents/pharmacology

OBJECTIVETo explore the role of prenatal exposure to lipopolysaccharides (LPS) on aortic morphology in the neonatal offspring rats.

METHODSTwelve pregnant rats were randomly divided into three groups: control group, LPS group, and PDTC (pyrrolidinedithiocarbamate, LPS+PDTC) group. The rats were intraperitoneally administered vehicle, LPS (0.79 mg/kg) , or LPS plus PDTC (100 mg/kg) , respectively. LPS was given on the 8th, 10th and 12th days, whereas vehicle and PDTC were given daily from the 8th to the 14th day during gestation. Histopathological alteration of the thoracic aorta was observed by hematoxylin-eosin staining and transmission electron microscopy, thoracic aortic mRNA and protein expression of connexin (Cx) molecules including Cx37, Cx40, Cx43 and Cx45 in offspring was detected by Real Time PCR and confocal laser-scanning microscope, respectively, offspring body weight was measure at day 1 and week 1.

RESULTSBody weight at 1 day and 1 week-old offspring was significantly lower in LPS group than in control group (P < 0.01), which were significantly higher in PDTC group compared to LPS group (P < 0.01): [1 day: control group (7.425 ± 0.146) g, LPS group (6.742 ± 0.128) g, PDTC group (7.137 ± 0.141) g; 1 week: control group (20.173 ± 3.982) g, LPS group (13.264 ± 2.581) g, PDTC group (17.863 ± 3.412) g]. In 1 week-old offspring of LPS group, the thoracic aortas exhibited lesions, including impaired endothelial cells, thickening and fibrous changes of intimae, and migration and proliferation of vascular smooth muscle cells; the number of gap junction was decreased versus control group and pathological changes were similar between PDTC group and LPS group. Cx43 protein expression in LPS group was obviously lower than in control group and which could be partly reversed in PDTC group. Expression of Cx43 mRNA was significantly lower in 1 day and 1 week offspring of LPS group compared to control group (P < 0.05), which could be reversed in PDTC group (P < 0.05) (1 day: control group 1.530 ± 0.296, LPS group 1.226 ± 0.209, PDTC group 1.619 ± 0.324; 1 week: control group 9.357 ± 1.917, LPS group 7.204 ± 1.165, PDTC group 9.271 ± 1.514).

CONCLUSIONOur results indicate that maternal LPS exposure during pregnancy leads to vascular changes in neonatal offspring which might increase the susceptibility to adult hypertension.

Animals ; Aorta, Thoracic ; drug effects ; pathology ; Connexin 43 ; metabolism ; Female ; Lipopolysaccharides ; toxicity ; Maternal Exposure ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley

AIMTo observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected.

METHODSHealthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected.

RESULTSCompared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P < 0.01), the format and percentage that capillary dilated declined significantly (P < 0.05), after treatment with Tongxinluo powder, the effect of Ach on isolated rat thoracic aorta in vitro was improved obviously (p < 0.01), and the format and percentage that capillary dilated were increased compared with model group; comparing with the control group, the level of Ang II and ET, TXA2 in plasm increased obviously (P < 0.05, P < 0.01), while the content of PGI2 depressed manifestly (P < 0.05), at the same time, both content of NO and activity of SOD, (GSH-PX declined obviously (P < 0.001, P < 0.05). After treatment with Tongxinluo powder, the level of ET, AngII and TXA2 reduced significantly in different degree (P < 0.01), while the content of PGI2 appeared stepping up notably (P < 0.01), and both activity of SOD and NO level increased obviously (P < 0.01, P < 0.05).

CONCLUSION(1) The high homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.

Animals ; Aorta ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Homocysteine ; antagonists & inhibitors ; pharmacology ; Male ; Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo study the effects of the divided functional recipes of Dahuang Zhechong pill( DHZCP) on atherosclerosis in rabbits.

METHODThe atherosclerotic model was established by the combination of hypercholesterol feeding and immune-injured endothelium in rabbits. Male New Zealand rabbits were randomly divided into nine groups: normal group, model group, Danshen group (0. 5 g x kg(-1) ), the low-dose(0. 5 g x kg(-1) ) and high-dose( 1.0 g - kg(-1) ) groups of the first divided recipe, the low-dose(0. 75 g x kg-' ) and high-dose(1. 5 g x kg(-1)) groups of the second divided recipe, the low-dose(0. 8 g x kg(-1) ) and high-dose( 1.6 g x kg(-1) ) groups of the third divided recipe. The effects of the divided functional recipes of DHZCP were observed in macropathology, histopathology and ultrastructure. Image analyzing system was used to determine atherosclerotic plaque area, intima thickness(IT) and intima-media thickness(IMT) in rabbit aorta.

RESULTThe divided functional recipes of DHZCP could significantly decreased the deposit of lipid and the atherosclerotic plaque area in aorta intima, relieve the histopathological changes of atherosclerosis, and inhibited the proliferation of vascular smooth muscle cells and collagen to reduce pachynsis of vascular intima. The divided functional recipes of DHZCP also reduced IT, IMT and IT/MT and reversed the contractive vascular remodeling.

CONCLUSIONThe divided functional recipes of DHZCP produce the different anti-atherosclerotic action, among which the first divided functional recipe exhibits more effective action.

Animals ; Aorta ; drug effects ; pathology ; ultrastructure ; Atherosclerosis ; pathology ; prevention & control ; Cell Proliferation ; drug effects ; Cockroaches ; chemistry ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Male ; Medicine, Chinese Traditional ; Microscopy, Electron ; Myocytes, Smooth Muscle ; drug effects ; pathology ; ultrastructure ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rheum ; chemistry ; Tunica Intima ; drug effects ; pathology

OBJECTIVETo investigate the influence of nitroglycerin tolerance (NT) on arterial ischemia (90 min) and reperfusion (120 min).

METHODSMale Sprague-Dawley rats were infused with nitroglycerin (GTN) or saline for 12 h and ascending aorta was rapidly isolated. The isolated aorta was subjected to one of the following treatments: stimulative ischemia/reperfusion, stimulative ischemia/reperfusion (I/R) plus glutathione (GSH, 0.1 mmol/L) during reperfusion, or control solution (Kreb's solution for 3.5 h).

RESULTSCompared with I/R group, contractile function, vasorelaxation responses to Ach, NO production were significantly decreased and CK, LDH activity as well as nitrotyrosine formation in reperfusion solution were significantly increased in I/R + NT group and these effects could be prevented with addition of GSH in I/R + NT aortas.

CONCLUSIONSOur results demonstrated that NT could aggravate arterial I/R injury by increasing the production of ONOO- and GSH may play a cardioprotective role against NT-induced myocardial injury by attenuating the formation of ONOO-.

Animals ; Aorta ; drug effects ; Drug Tolerance ; Glutathione ; metabolism ; In Vitro Techniques ; Male ; Nitroglycerin ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology ; physiopathology ; Vasoconstriction

OBJECTIVETo observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice.

METHODSThirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method.

RESULTSAs compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups.

CONCLUSIONHXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.

Animals ; Aorta ; drug effects ; pathology ; Apolipoproteins E ; deficiency ; genetics ; Atherosclerosis ; pathology ; Biological Transport ; drug effects ; Caveolin 1 ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plaque, Atherosclerotic ; pathology ; Receptors, Scavenger ; metabolism

OBJECTIVETo investigate the effects of Qushuanling Capsule ( QSLC) on thrombus formation and platelet aggregation in rats.

METHODSArteriovenous bypass, venous thrombosis, and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1α (6-keto-PGF1α) in rat plasma and aortic walls, were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.

RESULTSAfter oral administration with QSLC for 7 days, arteriovenous bypass thrombosis was obviously suppressed compared with the model group, venous thrombosis was also obviously suppressed, rat behaviors were obviously improved, and brain infarct size as well as water content were also reduced. The platelet aggregation induced by ADP or thrombin was inhibited by QSLC, but the drug had no effect on AA-induced platelet aggregation and content of TXB(2) and 6-keto-PGF1α in plasma and the aortic wall.

CONCLUSIONThese results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases, and that its mechanism of action may be related to inhibition of platelet aggregation.

6-Ketoprostaglandin F1 alpha ; blood ; Adenosine Diphosphate ; pharmacology ; Animals ; Aorta ; drug effects ; metabolism ; pathology ; Cerebral Infarction ; blood ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Middle Cerebral Artery ; drug effects ; pathology ; Platelet Aggregation ; drug effects ; Rats ; Rats, Sprague-Dawley ; Thrombosis ; drug therapy ; pathology ; Thromboxane B2 ; blood ; Venous Thrombosis ; drug therapy ; pathology