No abstract available.
Basilar Artery* ; Rabbits* ; Vasoconstrictor Agents* ; Vasodilator Agents*

Animals ; Humans ; Pyrazines ; pharmacology ; Vasodilator Agents

Since a cyclooxygenase 2 (COX-2) inhibitor can reduce infarct size and improve contractility in ischemic myocardium, the aim of the present study was to explore whether COX-2 inhibitor nimesulide could protect myocardial function against oxidative stress injury in rat hearts, and to investigate the underlying mechanisms. The isolated rat hearts perfused by Langendorff method were exposed to 140 mumol/L of H2O2, and the cardiac contractility was measured. Then, the responses of coronary arteries, precontracted with U-46619, to the endothelium-dependent vasodilator serotonin (5-HT) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were evaluated. The results were as follows: (1) In hearts exposed to H2O2 for 20 min, the left ventricular developed pressure [LVDP, (54.8 +/- 4.0)%] and maximal rate of rise/fall of ventricular pressure [+/-dp/dt(max), (50.8 +/- 3.1)% and (46.2 +/- 2.9) %] were reduced compared with that in the control group (100%). After pretreatment with nimesulide (5 mumol/L) for 10 min before H2O2 perfusion, LVDP and +/-dp/dt(max) were enhanced to (79.9 +/- 2.8)%, (80.3 +/- 2.6)% and (81.4 +/- 2.6)%, respectively (P<0.01), and this was partially abolished by the nitric oxide synthase (NOS) inhibitor L-NAME [(60.2 +/- 2.1)%, (63.9 +/- 2.4)% and (63.1 +/- 2.9)%, respectively, P<0.01]. (2) The vasodilatation induced by 5-HT and SNP in H2O2-treated group was significantly less than that in the control group. Pretreatment with nimesulide for 10 min antagonized the decrease of endothelium-dependent vasodilatation in H2O2-treated group [(-22.2 +/- 4.2) % vs (-6.0 +/- 2.5) %, P<0.01], but had no effect on the decline of endothelium-independent vasodilatation [(-2.0 +/- 1.8)% vs (-7.0 +/- 3.5) %, P>0.05]. (3) Pretreatment with nimesulide for 10 min increased the NO production in H2O2-treated hearts [(2.63 +/- 0.40) vs (1.36 +/- 0.23) nmol/g protein, P<0.05], and this was inhibited by L-NAME. (4) Pretreatment with the selective COX-1 inhibitor piroxicam had no effect on LVDP and +/-dp/dt(max) in isolated hearts exposed to H2O2, but the left ventricular end diastolic pressure (LVEDP) was much higher than that in the group treated with H2O2 alone. Piroxicam did not influence the coronary resistance in H2O2-treated rat hearts. These data suggest that the COX-2 inhibitor nimesulide improves myocardial function in rat hearts suffering from oxidative stress, and this may be through an improvement in endothelium-dependent arterial relaxation and an enhancement of NO production in rat heart.
Animals ; Coronary Vessels ; Cyclooxygenase 2 Inhibitors ; Endothelium, Vascular ; Endothelium-Dependent Relaxing Factors ; Heart ; drug effects ; Hydrogen Peroxide ; Myocardial Reperfusion Injury ; Myocardium ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Sulfonamides ; pharmacology ; Vasodilation ; Vasodilator Agents

OBJECTIVETo investigate the effect of Astragalus membranaceus (AM) on endothelial-dependent (EDV) and non- dependent (EIV) vascular relaxation in ex vivo thoracic aortic rings of obese rats.

METHODSFifteen SD rats were randomized into 3 equal groups, namely the control group fed with normal chow, obese group with high-fat chow, and AM intervention group fed with high-fat chow and daily AM gavage. The rats were sacrificed after 6 weeks of feeding, and the aortic rings were dissected and cut into 3-mm rings. The response to acethylcholine (Ach) and sodium nitroprusside (SNP) were examined in organ bath. In ex vivo study, the aortic rings obtained from the control group and obese group were incubated with AM or vehicle for 3 h in organ bath before testing the EDV and EIV. The body weight and weight of the visceral fat in each group were recorded.

RESULTSThe weight of visceral fat was greater in the obese group than in the control group, and a 6-week AM treatment significantly reduced the fat tissue due to high-fat diet. The maximum EDV value was (87.0 - or + 3.5)% in the control group, (54.8 - or + 7.8)% in the obese group, and (69.8 - or + 5.7)% in AM intervention group; the EIV values were comparable between the 3 groups. After incubation with AM, the maximum EDV values of aortic rings obtained from the obese group were significantly increased from (55.6 - or + 8.3)% to (85.1 - or + 4.5)%.

CONCLUSIONAM can improve endothelial dysfunction in obese rats, and the mechanism involves improved insulin resistance and increased endothelium-derived NO productor function.

Animals ; Aorta, Thoracic ; pathology ; Astragalus membranaceus ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Endothelium-Dependent Relaxing Factors ; therapeutic use ; In Vitro Techniques ; Insulin Resistance ; Male ; Obesity ; physiopathology ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Vasodilator Agents ; pharmacology

Animals ; Enflurane* ; Halothane* ; Isoflurane* ; Rats* ; Relaxation* ; Vasodilator Agents*

Interleukin-2 (IL-2) therapy often results in potentially life-threatening side effects including hypotension. However, the mechanism has not been completely elucidated. In order to determine whether IL-2 modifies vascular tone, we investigated the effect of IL-2 on rat thoracic aorta rings and the underlying mechanisms. Effects of IL-2 on the contraction of high KCl and phenylephrine (PE) preconstricted rat thoracic aorta with or without endothelium were determined by organ bath technique. To explore the mechanism, nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), guanylyl cyclase inhibitor methylene blue, and cyclooxygenase inhibitor indomethacin were used. IL-2 (10-1000 U/ml) caused concentration-dependent relaxation of aorta rings preconstricted with PE (10 micromol/L) in endothelium-intact rings, but had no effect on KCl (120 mmol/L) preconstricted rings. Removal of the endothelium, or pretreatment with L-NAME (0.1 mmol/L) or methylene blue (10 micromol/L) or indomethacin (10 micromol/L), inhibited the relaxation of IL-2. The results indicate that the relaxation by IL-2 in rat aorta ring is endothelium-dependent and is possibly mediated by the NO-guanylyl cyclase pathway and cyclooxygenase-dependent pathway.
Animals ; Aorta, Thoracic ; drug effects ; physiology ; Endothelium, Vascular ; drug effects ; Endothelium-Dependent Relaxing Factors ; pharmacology ; Guanylate Cyclase ; metabolism ; In Vitro Techniques ; Interleukin-2 ; pharmacology ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Prostaglandin-Endoperoxide Synthases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

Nicardipine is a potent coronary and systemic vasodilator without depression of ventricular function. We investigated the changes in local myocardial perfusion (LMP) according to the nicardipine administration after coronary reperfusion in a beating canine model. A Doppler probe was placed around the left anterior descending coronary artery (LAD) and thermal diffusion microprobe was implanted in the myocardium perfused by the exposed LAD. To define the nicardipine effects, we compared the two groups (control group, n=7 vs nicardipine group, n=7). In nicardipine group, 5 microgram/kg/min nicardipine was infused continuously. After the release of the LAD occlusion, LAD blood flow were increased compared to the baseline of both groups. However, there was no difference between groups in the LAD blood flow. The LMP after LAD reperfusion did not recover to the baseline level until 30 min after LAD reperfusion in control group (74%, 52% and 70% at 10, 20 and 30 min after LAD reperfusion, respectively). In nicardipine group, however, the LMP recovered to the baseline level at 20 min (99%), and increased more than the baseline level at 30 min (141%) after LAD reperfusion. Our findings suggest that the nicardipine augments the LMP following the release of a coronary occlusion.
Animals ; Coronary Circulation/drug effects* ; Dogs ; Drug Evaluation, Preclinical ; Myocardial Reperfusion* ; Myocardial Reperfusion Injury/prevention & control* ; Nicardipine/pharmacology* ; Nicardipine/therapeutic use ; Vasodilator Agents/pharmacology* ; Vasodilator Agents/therapeutic use

Pulmonary hypertension is an uncommon but serious complication of systemic lupus erythematosis (SLE).Usually its outcomes are ominous and may progress to heart failure and even sudden death.The pathophysiology is still unknown, but several mechanisms,such as pneumonitis,vasculitis,thromboembolism or thrombosis in situ have been proposed.There is no definitive therapy for this condition.Although supportive measures with vasodilators remain the mainstay of treatment,the responses are generally disappointing. We describe a case of improvement of pulmonary hypertension in SLE treated with cyclophosphamide pulse therapy as documented by hemodynamic data. Immunosuppressive treatment with cyclophosphamide was effective in this condition,suggested an immune mediated pathogenesis.
Cyclophosphamide* ; Heart Failure ; Hemodynamics ; Hypertension, Pulmonary* ; Lupus Erythematosus, Systemic* ; Thrombosis ; Vasodilator Agents

BACKGROUND: The measurement of transepidermal water loss(TEWL) is widely used in evaluating the stratum corneum barrier function. It is also possible to evaluate the penetration of substances into the skin as an additional parameter of the straturn corneum barrier function. OBJECTIVE: The purpose of the present study is to investigate ihe relationship between TEWL and the percutaneous absorptic n of methyl nicotinate(MN) in the normal and acute perturbative state of the epidermal barrier. METHOD: Vascular response 10 MN penetration were rneasured by both laser Doppler flowmetry (LDF) and visual erythema oii the forearms of 30 healthy volunteers. Stratum corneum of the ar ea of 2x10cm on the volar for earm was removed by repeated tape stripping when TEWL reached 12-30g/rnh measured with Evaporimeter. The left forearm received no treatrnent as a control site. Each time the profile of the vascular response to MN penetration was analysed using the following parameters:the 1ag-time between MN application and initial response(T0), the time between MN application and maximal response(T(max)), and the rnaximal response(LDF), the time between MN application and initial visual erythema(VT0), and the time between MN application and maxirnum visual erythema(VT(max)). RESULTS: The data showed a negative correlation between TEWL and T0(r=-12.89, p<0.001), TEWL and Tmax=(r=-14.87, p<0.001), and TEWL and VT0(r= -3.99, p<0.001), TEWL and VTmax(r = -9.29, p<0.001). And there was a positive correlation between VT0 and T0(r=1.19, p<0.001), and between VTmax and Tmax(r=1.05, p<0.001). However, there was no detectable correlation between TEWL and LDFmax(p>0.05). CONCLUSION: Vascular response to percutaneous absorption of MN measured by LDF as well as TEWL is a useful non-invasiv method for objective evaluation of the stratum corneum barrier function. In addition, visual erythema induced by topical vasodilators such as MN is also a good method for skin barrier function assessment.
Erythema ; Forearm ; Healthy Volunteers ; Laser-Doppler Flowmetry ; Niacin* ; Skin Absorption* ; Skin* ; Vasodilator Agents

Acute heart failure (HF) is commonly encountered in the emergency department and thus, the hospital admissions for worsening HF are increasing. However, the patients presenting with acute HF are heterogenous and complex at high risk of morbidity and mortality. The main goals of treatment for hospitalized patients with HF are to restore euvolemia and to maintain the hemodynamic status without causing adverse events. Currently, the recommendations are usually based on a clinical factor considering the initial systolic blood pressure and other symptoms. Accordingly, initial managements in the hospital generally include diuretics, vasodilators, morphine, and inotropic agents, all of which have been considered as traditional therapies. These agents should mainly increase cardiac output and improve symptoms, and importantly it should improve the clinical outcomes. The aim of this review is to describe the available and new pharmacologic drugs for patients presenting with acute HF.
Blood Pressure ; Cardiac Output ; Diuretics ; Emergencies ; Heart ; Heart Failure ; Hemodynamics ; Humans ; Morphine ; Vasodilator Agents