BACKGROUND/AIMS: DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Corydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. METHODS: Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. RESULTS: In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. CONCLUSIONS: The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.
Analgesics/administration & dosage/*pharmacology ; Animals ; Arterial Pressure/drug effects ; Colon, Descending/physiology ; Dilatation/methods ; Gastrointestinal Agents/administration & dosage/*pharmacology ; Male ; Pain Threshold/drug effects ; Plant Preparations/administration & dosage/*pharmacology ; Rats, Sprague-Dawley ; Visceral Pain/physiopathology/*prevention & control

OBJECTIVETo compare the effects of common carotid artery and femoral vein administration of propofol for electrocerebral silence (ES) on circulatory and respiratory function and the dosage of propofol required during ES in dogs.

METHODSEight dogs were anesthetized by common carotid arterial and femoral vein administration of propofol for ES for 1 h. The time of consciousness loss and recovery, dose of propofol during ES, mean arterial pressure, heart rate, respiration rate, end-tidal carbon dioxide, SpO2, cerebral state index (CSI) and anal temperature were continuously monitored. Changes in the outcome variables were analyzed at 7 time points, namely the baseline, upon loss of consciousness, at 10 s, 30 min and 1 h of CSI=0, and recovery of CSI and consciousness.

RESULTSCarotid artery propofol administration produced ES with only half of the dose for intravenous administration. Compared with the baseline values, the mean artery pressure and respiration rate remained unchanged or decreased transiently during ES with carotid artery propofol administration. In contrast, intravenous propofol administration resulted in systemic hypotension and severe respiratory depression.

CONCLUSIONCarotid artery propofol administration produces ES with a much smaller dose than intravenous propofol administration without causing systemic hypotension or respiratory depression.

Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Blood Circulation ; drug effects ; Blood Pressure ; drug effects ; Brain ; blood supply ; drug effects ; physiology ; Carotid Arteries ; Consciousness ; Dogs ; Female ; Femoral Vein ; Heart Rate ; drug effects ; Injections, Intra-Arterial ; Injections, Intravenous ; Male ; Propofol ; administration & dosage ; pharmacology ; Respiration ; drug effects

To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease (COPD).A total of 75 male Wistar rats were randomly divided into control group (group CN), model group (group M), low-dose curcumin group (group CL), medium-dose curcumin group (group CM) and high-dose curcumin group (group CH). HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen (PCNA), apoptosis-related protein Bcl-2 and Bax were detected by immunohistochemical staining. TUNEL kit was used to analyze the effects of curcumin on apoptosis of smooth muscle cells, and the protein expressions of SOCS-3/JAK2/STAT pathway in lung tissues were determined by western blot.Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVMI) in group M were significantly higher than those in group CN, group CH and group CM (all<0.05). HE staining and TUNEL kit test showed that the number of pulmonary artery smooth muscle cells had a significant increase in group M, while the pulmonary artery tube became thin, and the smooth muscle cells shrinked in group CM and group CH. Immunohistochemistry showed that PCNA and Bcl-2 in group M were significantly higher than those in group CN (all<0.05), while Bax expression was significantly lower than that in group CN (<0.05). PCNA in group CM and group CH were significantly lower than that in group M (all<0.05), while Bax expression was significantly higher than that in group M (<0.05). Western blot showed that SOCS-3 protein was significantly decreased in group M, while the p-JAK2, p-STAT1, p-STAT3 were significantly increased (all<0.05). Compared with group M, SOCS-3 protein in group CM and group CH were significantly increased (all<0.05), while the p-JAK2, p-STAT3 were significantly reduced (all<0.05).Curcumin could promote the apoptosis of smooth muscle cells in rats with COPD, and improve the mean pulmonary artery pressure and RVMI through stimulating SOCS-3/JAK2/STAT signaling pathway.
Animals ; Apoptosis ; drug effects ; physiology ; Arterial Pressure ; drug effects ; physiology ; Curcumin ; pharmacology ; Hypertrophy, Right Ventricular ; pathology ; physiopathology ; Janus Kinase 2 ; drug effects ; physiology ; Lung ; chemistry ; drug effects ; Male ; Myocytes, Smooth Muscle ; drug effects ; pathology ; Proliferating Cell Nuclear Antigen ; drug effects ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; drug effects ; metabolism ; Pulmonary Artery ; drug effects ; pathology ; Pulmonary Disease, Chronic Obstructive ; pathology ; physiopathology ; Rats ; Rats, Wistar ; STAT Transcription Factors ; Suppressor of Cytokine Signaling 3 Protein ; drug effects ; physiology ; Ventricular Pressure ; drug effects ; bcl-2-Associated X Protein ; drug effects ; metabolism

BACKGROUND/AIMS: We assessed the efficacy and safety of bosentan in patients with pulmonary arterial hypertension (PAH). METHODS: We surveyed randomized controlled trials (RCTs) of the efficacy and safety of bosentan in patients with PAH using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. Results are presented as odds ratios (ORs) or weighted mean differences (WMDs). RESULTS: Meta-analysis of seven RCTs including a total of 410 patients and 296 controls revealed that the 6-minute work distance was significantly higher in the bosentan group than in the placebo group (WMD, 46.19; 95% confidence interval [CI], 21.20 to 71.19; p = 2.9 x 10(-5)). Compared with the placebo, bosentan significantly reduced the mean pulmonary arterial pressure in patients with PAH (WMD, -6.026; 95% CI, -8.785 to -3.268, p = 1.8 x 10(-6)). The bosentan therapy group worsened less clinically than the placebo group (OR, 0.252; 95% CI, 0.140 to 0.454; p = 4.6 x 10(-7)). The incidence of serious adverse events did not differ between the bosentan and placebo groups (OR, 0.948; 95% CI, 0.556 to 1.614; p = 0.843). However, the results of the abnormal liver function test (LFT) were significantly higher in the bosentan group than in the placebo group (OR, 2.312; 95% CI, 1.020 to 5.241; p = 0.045). CONCLUSIONS: This meta-analysis shows that bosentan can treat PAH effectively. However, bosentan increased the incidence of abnormal LFT results compared with the placebo.
Antihypertensive Agents/adverse effects/*therapeutic use ; Arterial Pressure/*drug effects ; Humans ; Hypertension, Pulmonary/diagnosis/*drug therapy/physiopathology ; Liver/drug effects/physiopathology ; Liver Function Tests ; Odds Ratio ; Pulmonary Artery/*drug effects/physiopathology ; Risk Factors ; Sulfonamides/adverse effects/*therapeutic use ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate the effects of simvastatin on atherosclerosis and central aortic pressure in ApoE-knockout (ApoE-/-) mice.

METHODSTen 5-week-old male ApoE-/- mice and 5 C57 mice were fed with high-lipid diet for 3 weeks, and then C57 mice (WT group) and 5 ApoE-/- mice (ApoE-/- group) were given 1% carboxymethyl cellulose solution (8 ml·kg-1·d-1), and another 5 ApoE-/- mice (ApoE-/-/S group) were given simvastatin solution (50 mg·kg-1·d-1) by gavege for 3 weeks. The areas of atherosclerotic lesion in aortic root, central aortic pressure and serum lipid levels were examined.

RESULTSNo atherosclerotic plaques were observed in WT group. Compared with ApoE-/- group, simvastatin significantly decreased atherosclerotic lesion area in aortic root (89 818.05±16 980.93 μm2 vs 34 937.01±13 280.65 μm2, P<0.05). The systolic pressure (SP), mean arterial pressure (MAP), pulse pressure (PP) and diastolic pressure (DP) of central aortic pressure were significantly increased in ApoE-/- group compared with those in WT group (P<0.05). Compared to ApoE-/- group, the SP, MAP and PP of central aortic pressure were significantly reduced in ApoE-/-/S group (P<0.05). SP and MAP of central aortic pressure were positively correlated with atherosclerotic lesion area (SP: r=0.7152, P=0.0461; PP: r=0.7594， P=0.0288). Compared with WT group, serum triglyceride, total cholesterol and low-density lipoprotein levels were markedly increased in ApoE-/- group (P<0.05). Serum high-density lipoprotein level was decreased in ApoE-/- group compared with WT group. No differences in serum triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein levels were found between ApoE-/- group and ApoE-/-/S group.

CONCLUSIONSimvastatin can attenuate atherosclerosis of aorta in ApoE-/- mice, which is associated with the reduced central aortic systolic pressure but not with the serum lipids levels.

Animals ; Apolipoproteins E ; genetics ; Arterial Pressure ; drug effects ; Atherosclerosis ; drug therapy ; genetics ; physiopathology ; Cholesterol ; blood ; Disease Models, Animal ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Mice ; Mice, Knockout ; Simvastatin ; pharmacology ; Triglycerides ; blood

Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.
Animals ; Antioxidants ; therapeutic use ; Arterial Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Infusions, Intraventricular ; Male ; Metformin ; administration & dosage ; pharmacology ; Neurotransmitter Agents ; metabolism ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Rats ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

BACKGROUNDThe clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.

METHODSWe analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.

RESULTSThe rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).

CONCLUSIONSThe rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.

Administration, Inhalation ; Adult ; Aged ; Arterial Pressure ; drug effects ; Atrial Natriuretic Factor ; metabolism ; Calcium Channel Blockers ; administration & dosage ; therapeutic use ; Endarterectomy ; Familial Primary Pulmonary Hypertension ; drug therapy ; physiopathology ; Female ; Hemodynamics ; drug effects ; Humans ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Iloprost ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Protein Precursors ; metabolism ; Retrospective Studies ; Software ; Vasodilator Agents ; administration & dosage ; therapeutic use

No abstract available.
Acute Disease ; Aged ; Anticoagulants/therapeutic use ; Antihypertensive Agents/therapeutic use ; Aortic Diseases/diagnosis/*etiology/physiopathology/therapy ; Aortography/methods ; Arterial Pressure ; Female ; Fibrinolytic Agents/*adverse effects ; Hematoma/diagnosis/*etiology/physiopathology/therapy ; Humans ; Pulmonary Embolism/diagnosis/*drug therapy ; Recombinant Proteins/adverse effects ; Thrombolytic Therapy/*adverse effects ; Tissue Plasminogen Activator/*adverse effects ; Tomography, X-Ray Computed ; Treatment Outcome ; Vena Cava Filters

We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg^-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg^-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg^-1 LIMK2i and 20.0 mg kg^-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.
Animals ; Apoptosis/drug effects* ; Arterial Pressure ; Electric Stimulation ; Erectile Dysfunction/pathology* ; Lim Kinases/antagonists & inhibitors* ; Male ; Nerve Crush ; Nitric Oxide Synthase Type III/metabolism* ; Penis/pathology* ; Peripheral Nerve Injuries/pathology* ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Phosphorylation ; Pyrimidines/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Sulfonamides/therapeutic use*