BACKGROUNDObstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension. The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin II (Ang II) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK), myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).

METHODSMale Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles. Phosphorylation of ERK1/2, MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 µmol/L).

RESULTSCIH-exposure resulted in more body weight gain and elevated blood pressure, which could be attenuated by pretreatment with PD98059. Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang II (Emax: (138.56 ± 5.78)% versus (98.45±5.31)% of KCl; pD2: 7.98 ± 0.14 versus 8.14 ± 0.05, respectively). CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2 increased). CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC. In parallel to greater increases in phosphorylation of ERK1/2, MYPT1 and MLC, Ang II-induced aortic constriction was significantly enhanced in CIH rats, which was largely reversed by PD98059. However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.

CONCLUSIONThese data suggest that CIH exposure results in aortic hyperresponsiveness to Ang II, presumably owing to more activated ERK1/2 signaling pathway.

Angiotensin II ; pharmacology ; Animals ; Aorta ; drug effects ; Flavonoids ; pharmacology ; Hypoxia ; physiopathology ; MAP Kinase Signaling System ; drug effects ; Male ; Phosphorylation ; drug effects ; Rats ; Rats, Wistar ; Vasoconstriction ; drug effects

OBJECTIVETo observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms.

METHODSYoung male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly.

RESULTSCoptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction.

CONCLUSIONCoptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP-sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane.

Animals ; Aorta, Thoracic ; physiopathology ; Calcium ; metabolism ; Coptis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Hypoxia ; physiopathology ; In Vitro Techniques ; KATP Channels ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects

Acidosis ; complications ; physiopathology ; Animals ; Aorta, Thoracic ; drug effects ; physiopathology ; Dopamine ; pharmacology ; In Vitro Techniques ; Male ; Rats ; Rats, Wistar ; Shock, Septic ; complications ; physiopathology ; Sympathomimetics ; pharmacology

OBJECTIVETo explore the effect of the level of lipid peroxidation and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in thoracic aorta of hyperlipemia (HL) rats.

METHODSHL rats were given BH4 chronically. The opening angle in the zero-stress state and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image 8, 16, and 24 week-old respectively.

RESULTSTreating with BH4 chronically from 8 week-old in HL rats, there was a significant increase in the zero-stress state of opening angle of thoracic aorta. The P-D curve of mesenteric artery moved upward.

CONCLUSIONTreating with BH4 prevented the structure and function of artery from abnormal changing, and attenuated lipid peroxidation in HL rats.

Animals ; Aorta, Thoracic ; metabolism ; physiopathology ; Biomechanical Phenomena ; drug effects ; Biopterin ; analogs & derivatives ; therapeutic use ; Hyperlipidemias ; drug therapy ; Lipid Peroxidation ; drug effects ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of rhodiola on expression of vascular endothelial cell growth factor (VEGF) and angiogenesis in aortic atherosclerotic plaque of rabbits.

METHODSThirty male New Zealand rabbits were randomly divided into 3 groups equally, i. e. the control group (A) fed with common diet and treated with distilled water, the high fat diet group (B) and the rhodiola group (C) fed with diet containing 1.5% cholesterol and treated respectively with distilled water and rhodiola (1 mL/kg per day), all the treatments were administered via gastrogavage once a day for 9 successive weeks. Level of blood lipids in various groups was determined and compared at the end of the experiment. Meanwhile, the tissue sample of aorta was taken for observation through HE and Sudan red staining, for detecting the CD34 positive response intensity by immunohistochemical staining and the VEGF expression by Real-time fluorescent quantitative PCR and Western blot.

RESULTSDetermination of blood lipids showed that in Group C, TC was 42.01 +/- 1.99 mmol/L, TG 4.83 +/- 0.75 mmol/L and LDL-C 38.40 +/- 0.74 mmol/L, all lower than those in Group B (70.74 +/- 2.66 mmol/L, 8.75 +/- 0.78 mmol/L and 51.05 +/- 0.34 mmol/L, respectively), showing statistical difference between groups (P < 0.05). The intima/media tunica thickness ratio and the CD34 positive area of plaque in Group C were all lower than those in Group B (0.35 +/- 0.03 vs 0.43 +/- 0.03 and 29.12 +/- 2.56% vs 39.28 +/- 3.48%, P <0.05). Besides, the VEGF expression in atherosclerotic plaque was also lower in Group C than that in Group B.

CONCLUSIONRhodiola has the effects of inhibiting atherosclerosis formation, decreasing the VEGF expression and suppressing the angiogenesis in the plaque.

Animals ; Aorta ; drug effects ; metabolism ; physiopathology ; Atherosclerosis ; drug therapy ; metabolism ; physiopathology ; Disease Models, Animal ; Gene Expression ; drug effects ; Humans ; Male ; Neovascularization, Physiologic ; drug effects ; Plant Extracts ; administration & dosage ; Random Allocation ; Rhodiola ; chemistry ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo study the modulatory effect of sulfur dioxide (SO(2)) on the accumulation of collagen type I and type III in the wall of aorta during spontaneously hypertensive rat (SHR) vascular remodeling.

METHODSEight male Wistar Kyoto rats at the age of 4 weeks with normal blood pressure were used as a control group. And sixteen male SHRs at the age of 4 weeks were randomly divided into an SHR control group and SHR + Na(2)SO(3)/NaHSO(3) (SO(2) donor) group. Na(2)SO(3)/NaHSO(3) solution was injected intraperitoneally everyday to the rats in the SHR + Na(2)SO(3)/NaHSO(3) group. After 5 weeks, the systemic blood pressure was measured. The weight ratio of left ventricle to the whole heart was also measured. The rat aorta was dyed with Hart's method. The morphometric parameters including outer radius, lumen radius and the wall thickness were calculated by Leica workstation. The plasma level of SO(2) was determined by HPLC method. The expressions of collagen type I and type III in aorta were detected by immunohistochemistry.

RESULTS(1) Compared with the WKY rat control group, the systolic blood pressure increased by 53%, the weight ratio of left ventricle to the whole heart increased by 6% but the plasma level of SO(2) decreased by 44% for rats in the SHR group (P < 0.01 or P < 0.05). Compared with the SHR control group, the systolic blood pressure decreased by 26%, but the plasma level of SO(2) increased by 28% (all P < 0.01) for rats in the SHR + Na(2)SO(3)/NaHSO(3) group. (2) Compared with the WKY rats, the ratio of media to lumen radius increased by 28% for SHR. Compared with the SHR group, the ratio of media to lumen radius decreased by 10% (P < 0.01) in rats of the SHR + Na(2)SO(3)/NaHSO(3) group. (3) Compared with rats in the WKY control group, collagen type I expression increased by 10% for rats in the SHR group (P < 0.01). Compared with the SHR group, however, the expression decreased by 58% for rats in the SHR + Na(2)SO(3)/NaHSO(3) group (P < 0.01). (4) Compared with rats in the WKY control group, the expression increased by 13% for rats in the hypoxia SHR group (P < 0.01); however, compared with rats in the SHR group, the expression decreased by 8% in the rats of the SHR +Na(2)SO(3)/NaHSO(3) group (P < 0.01).

CONCLUSIONSIn the process of SHR vascular collagen remodeling in the rats, SO(2) could inhibit the abnormal accumulation of collagen type I and type III in the wall of aorta. This effect may be one of the mechanisms by which SO(2) ameliorates SHR vascular remodeling.

Animals ; Aorta, Thoracic ; drug effects ; metabolism ; physiopathology ; Blood Pressure ; drug effects ; Collagen ; metabolism ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Sulfur Dioxide ; pharmacology

OBJECTIVETo study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content.

METHODThe pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3). RM6000 eight channel physiological recorder was used to record haemodynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson's stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxyproline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content.

RESULTSAfter 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augmnent plasma PGI2 content.

CONCLUSIONIPT can significantly reverse abdominal aorta binding/pressure-overload induced cardiac remodeling, its mechanism may contribute to binding K(ATP) channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion.

Animals ; Aorta, Abdominal ; surgery ; Constriction ; Endothelium, Vascular ; metabolism ; physiology ; Epoprostenol ; blood ; Hypertension ; blood ; physiopathology ; KATP Channels ; drug effects ; Male ; Propylamines ; pharmacology ; Rats ; Ventricular Remodeling ; drug effects

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

The purpose of the present study was to investigate the effect of melatonin (MT) on the abnormal reactivity of thoracic aorta and pulmonary artery induced by lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into four groups randomly: (1) Vehicle group; (2) LPS group: LPS (4 mg/kg, i.p.); (3) LPS+MT group: MT (5 mg/ml, i.p.) was given 30 min before LPS and 60 min after LPS (4 mg/kg ,i.p); (4) MT group: received two doses of MT, 90 min after the first injection of MT another dose of MT was given. Six hours after LPS injection,the rats were killed and both thoracic aortic rings (TARs) and pulmonary artery rings (PARs)were prepared. The reactivity of TARs and PARs in the four subgroups was tested separately. The contraction response to phenylephrine (PE) and the endothelium-dependent relaxation response (EDRR) to ACh were observed with the isolated artery ring technique. Concentration-response curves were generated with ACh or PE (1 x 10(-8) - 1 x 10(-5) mol/L). Superoxide dismutes (SOD) activity and the content of malondialhyde (MDA) in artery tissues were detected. For TARs, LPS significantly reduced the contraction response to PE compared with the vehicle group (P<0.01) and the curve of cumulative dose responses to PE in the LPS group shifted downward. Although EDRR to ACh in the LPS group had the tendency to decrease but still showed no significant difference compared with the vehicle group (P>0.05). For PARs, EDRR to ACh was depressed significantly in the LPS group (P<0.01), while no effect on contraction response to PE in the LPS group was observed, compared with the vehicle group (P> 0.05). Compared with the LPS group, TARs in the LPS+MT group exhibited an increased contraction response to PE, but were still lower than that in the vehicle group. Similarly, EDRR to ACh of PARs in the LPS+MT group was improved significantly and there was no difference between the LPS+MT group and the vehicle group. The vascular reactivity was unaffected in MT group compared with the vehicle group in both TARs and PARs. SOD activity in the LPS +MT group increased significantly and the content of MDA decreased markedly compared with the LPS group. These results suggest that MT may improve the vascular reactivity in endotoxemia rats due to its antioxidant properties.
Animals ; Aorta, Thoracic ; physiopathology ; Endotoxemia ; chemically induced ; physiopathology ; Free Radical Scavengers ; pharmacology ; Lipopolysaccharides ; Male ; Melatonin ; pharmacology ; Pulmonary Artery ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

AIMTo investigate the effects of atrial natriuretic peptide(ANP) on constriction and relaxation of pulmonary artery and aorta in endotoxemia rat in vitro.

METHODS24 male SD rats were randomly divided into 3 groups, control group, LPS group, ANP therapy group. These groups were injected physiologic salt water, lipopolysaccharide (LPS 2 mg/kg) and LPS + ANP(LPS 2 mg/kg, ANP 2 microg/kg) into vein respectively. After 4 hours, rats were exsanguinated to kill and aorta and pulmonary artery were separated from heart-lung for experiment of blood vessel rings. Constriction effects of aorta and pulmonary artery by norepinephrine (NE), relaxation of aorta and pulmonary artery by acetylcholine (ACh) and sodium nitroprusside SNP) observed by perfusion system in vitro.

RESULTSSensitiveness of NE-induced (10(-9)-10(-7) mol/L) constriction of aorta in LPS group was attenuated and EC50 was increased, but its strength (3 x 10(-7)-10(-6) mol/L) was greater comparing with control group (P < 0.01). In ANP group, the NE-induced contractility of aorta was similar to LPS group (P > 0.05). Comparing with control group, NE-induced constriction of pulmonary artery exposure to LPS was reinforced especially in 3 x 10(-7)-10(-6) mol/L of NE (P < 0.01), but its EC50 was obviously higher (P <0.05). There was no significant difference between ANP group and control group in constriction of pulmonary artery (P > 0.05). Relaxation and sensitiveness of aorta and pulmonary artery exposure to LPS were evidently improved in ANP therapy group induced by ACh and SNP respectively (P < 0.01, P < 0.05) and their EC50 markedly decreased comparing with LPS group (P < 0.01, P < 0.05) respectively.

CONCLUSIONANP can suppress the reinforcing of NE-induced constriction of pulmonary artery exposure to LPS and partly or entirely reverse the attenuated relaxation of pulmonary artery and aorta induced by ACh and SNP in endotoxemia rats.

Acetylcholine ; pharmacology ; Animals ; Aorta ; drug effects ; physiology ; Atrial Natriuretic Factor ; pharmacology ; Endotoxemia ; physiopathology ; Male ; Nitroprusside ; pharmacology ; Norepinephrine ; pharmacology ; Pulmonary Artery ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects