3.COX-2 inhibitor nimesulide protects rat heart against oxidative stress by improving endothelial function and enhancing NO production.
Ping-Ping LV ; Ying FAN ; Wen-Liang CHEN ; Yue-Liang SHEN ; Li ZHU ; Lin-Lin WANG ; Ying-Ying CHEN
Acta Physiologica Sinica 2007;59(5):674-680
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
4.Astragalus membranaceus improves endothelial-dependent vasodilator function in obese rats.
Ming-rui LI ; Ye-rong YU ; Gang DENG
Journal of Southern Medical University 2010;30(1):7-10
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
6.Interleukin-2 induced endothelium-dependent relaxation of rat thoracic aorta.
Chun-Mei CAO ; Song YE ; Hu YU ; Qing-Sheng XU ; Zhi-Guo YE ; Yue-Liang SHEN ; Yuan LU ; Qiang XIA
Acta Physiologica Sinica 2003;55(1):19-23
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
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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
7.Nicardipine Augments Local Myocardial Perfusion after Coronary Artery Reperfusion in Dogs.
Journal of Korean Medical Science 2003;18(1):23-26
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
8.Digital Sympathectomy for Treatment of Raynaud's Syndrome.
Se Whan RHEE ; Hee Chang AHN ; M Seung Suk CHOI ; Chang Yeon KIM
Journal of the Korean Society of Plastic and Reconstructive Surgeons 2005;32(4):479-484
Raynaud's syndrome causes discolorization, ischemic claudication(pain) and necrosis of the digits through insufficiency in the circulation which is induced by intermittent spasms of the digital arteries. From January, 2002 to December, 2004, 10 patients were surgically treated for Raynaud's syndrome. 9 patients were female and 1 patient was male. 2 patients showed unilateral involvement, 8 patients were operated on both hands. 6 patients had necrotic changes on the finger tips due to the disease. Ages ranged from 21 to 60 with an average of 39.1. Ischemic pain, discolorization, and cold intolerance of the digits were the common symptoms. All patients were evaluated with color doppler before the surgery. Two different procedures were applied according to the severity of the disease: Patients with decreased circulation received, what we call a limited digital sympathectomy, i.e. stripping of the adventitia of the ulnar, radial and common digital arteries. An extended procedure, radical digital sympathectomy, was performed on patients with a complete block of circulation. Stripping of the adventitia in these patients also involved the proper digital arteries. Symptoms like discolorization, ischemic pain, and cold intolerance improved immediately after the surgery. The patients did not suffer from pain even with exposure to cold weather. We conclude that digital sympathectomy could improve the symptoms in Raynaud's patients who do not respond to conservative treatment such as calcium channel blocker and other vasodilators.
Adventitia
;
Arteries
;
Calcium Channels
;
Female
;
Fingers
;
Hand
;
Humans
;
Male
;
Necrosis
;
Spasm
;
Sympathectomy*
;
Vasodilator Agents
;
Weather
9.Clinical Study on the Effect of Intravenous Fluid to the BIood Pressure Change During Spinal Anesthesia .
Korean Journal of Anesthesiology 1972;5(1):19-23
Hypotension immediately after spinal anesthesia has been considered as the result of pre-ganglionic sympathetic paralysis and secondarily due to changes in cardiac output. And also the increase of vascular bed space about 20~25% was pointed ont during spinal anesthesia which was another cause of spinal hypotension. Same degree of increased vascular bed space was produced by vasodilators such as Dibenzyline and Arfonad. Therefore, vasopressors have been used as the drug of choice to prevent and treat this spinal hypotension. This study was attempted to combat the hypotension during spinal anesthesia by filling this increased vascular bed space with Lactated-Ringer's or Dextrose solution instead of giving vasopressors. Lactated-Ringer's or Dextrose solution was administered to 141 cases, before and immediately after. spinal anesthesia was performed. The given amount of fluid was about 12.5~15% of estimated total blood volume (Group A). And no intravenous fluid was given to 101 cases as control (Group B). Changes of the systolic, diastolic blood pressure and pulse rate were observed. In the Group A, significant changes of the systolic (t=2.52, p<0.02) and diastolic blood pressure (t=1.98, p<0. 05) was observed. The changes of pulse rate were found not significant in the both group series.
Anesthesia, Spinal*
;
Blood Pressure
;
Blood Volume
;
Cardiac Output
;
Glucose
;
Heart Rate
;
Hypotension
;
Paralysis
;
Phenoxybenzamine
;
Vasodilator Agents
10.Comparison of the Effects of Nitroglycerin and Nitroprusside on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung.
Korean Journal of Anesthesiology 1999;37(1):144-152
BACKGROUND: It has been reported that two common vasodilators, nitroglycerin (NTG) and sodium nitroprusside (SNP), inhibit regional HPV and decrease arterial oxygenation as a result. The purpose of the present study was, therefore, to determine the comparative effect of NTG and SNP on HPV in a rabbit model of isolated lung perfusion with exclusion of the influential factors on HPV. METHODS: In adult white rabbits (n=20), lungs were isolated and perfused with the constant pulmonary blood flow. The acid-base status and temperature of perfusate was also constantly maintained. Thirty minutes later, baseline hypoxic pressor response (HPR) was measured as the difference of pulmonary artery pressure (PAP) between a period of 95% hyperoxic gas inhalation and that of 3% hypoxic gas inhalation. ED50 of NTG and SNP was calculated from the hypoxic pressor response measured in the same way, according to changes of doses (0.5, 1.0, 2.0, and 5.0 microgram/kg). RESULTS: Both NTG and SNP significantly decreased the baseline PAP in the doses of 1.0 microgram/kg and above, and also decreased the HPR in a dose-related manner. ED50 of SNP was significantly lower than that of NTG. CONCLUSIONS: NTG and SNP dilated directly the pulmonary vasculature and inhibited HPV in a dose- related manner. SNP had a greater inhibiting effect on HPV than NTG.
Adult
;
Humans
;
Inhalation
;
Lung*
;
Nitroglycerin*
;
Nitroprusside*
;
Oxygen
;
Perfusion
;
Pulmonary Artery
;
Rabbits
;
Vasoconstriction*
;
Vasodilator Agents