橙皮素对离体大鼠胸主动脉环舒张作用和机制研究

目的：观察橙皮素（HSP）对大鼠离体胸主动脉血管反应性的影响及其可能的机制。方法采用离体血管平滑肌张力实验方法,观察 HSP对 Sprague Dawley（SD）大鼠离体胸主动脉环的作用,并探讨其作用机制。结果 HSP 对氯化钾（KCl）和去氧肾上腺素（PE）预收缩的血管环具有浓度依赖性的舒张作用。去内皮后,HSP 不同浓度梯度（10-5 mol/L,3×10-5 mol/L,6×10-5 mol/L,10-4 mol/L）的舒张血管作用减弱。结论 HSP对KCl和PE预收缩大鼠离体胸主动脉环具有浓度依赖性舒张作用。     

高山红景天乙醇提取液对大鼠离体胸主动脉环的舒张作用及机制探讨

目的观察高山红景天乙醇提取液对大鼠离体胸主动脉环的舒张作用,并探讨其机制。方法离体大鼠主动脉环,先用1.0 mmol/L苯肾上腺素（PE）和50 mmol/LKCl预收缩,然后加入0.5、1.0、2.0 mg/ml高山红景天乙醇提取液,调其终浓度为0.5、1.0、2.0 mg/ml,记录胸主动脉环张力变化。结果高山红景天乙醇提取液对PE和KC l预收缩的内皮完整的大鼠主动脉环有浓度依赖性的舒张作用。在无钙缓冲液（含EGTA）环境下,红景天预处理对PE导致的血管收缩有明显抑制作用。结论 高山红景天乙醇提取液可舒张大鼠离体主动脉环,其机制与其抑制血管平滑肌细胞内质网储存钙的释放有关。     

替米沙坦对大鼠离体胸主动脉环的舒张作用

目的观察替米沙坦对大鼠离体胸主动脉环张力的影响,并探讨其作用机制。方法采用离体血管张力实验方法。观察替米沙坦在1×10-9mol/L,1×10^-8mol/L,1×10^-7mol/L,1×10^-6mol/L,1×10^-5mol/L浓度时,对去甲肾上腺素（NE,1×10^-6mol/L）诱发大鼠离体胸主动脉环收缩的影响。观察内皮型一氧化氮合酶（eNOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME,10-4mol/L）、环氧合酶抑制剂吲哚美辛（10^-5mol/L）对替米沙坦作用的影响,以及替米沙坦对血管环外钙依赖性收缩和内钙依赖性收缩的影响。结果替米沙坦对NE（1×10^-6mol/L）预收缩的离体胸主动脉环产生浓度依赖性的舒张作用。用Indo预处理的血管环对替米沙坦的舒张反应与未经处理时比较无统计学意义（P〉0.05）。去内皮及L-NAME可显著减弱替米沙坦对血管环的舒张作用（P〈0.05）。替米沙坦对血管环外钙依赖性收缩和内钙依赖性收缩无影响作用。结论替米沙坦对NE预收缩的大鼠胸主动脉环具有浓度依赖性的舒张作用,其舒张反应可能有内皮依赖性,与内皮产生的NO有关,与前列环素的合成无关,不通过抑制外钙内流和内钙释放发挥舒张作用。     

地西泮对KCl预收缩老年大鼠胸主动脉的舒张作用

目的 观察地西泮(DZP)对老年大鼠离体胸主动脉血管反应性的影响及其可能机制.方法 采用离体血管张力实验方法 ,观察DZP对氯化钾(KCl)预收缩血管环的作用,并检测DZP对经无钙液预处理后的血管环的作用.结果 累积浓度的DZP对高浓度KCl引起的血管环收缩有浓度依赖性的舒张作用.去内皮后,低浓度(10-6mol/L,3×10-6mol/L,10-5mol/L,3×10-5mol/L)DZP的舒血管作用减弱.DZP预处理后,CaCl2收缩血管环的量效曲线非平行右下移.结论 DZP对KCl预收缩老年大鼠离体胸主动脉有浓度依赖性的舒张作用.     

吲哚布芬舒张血管的作用及机制研究

目的研究吲哚布芬对离体大鼠胸主动脉张力的影响,并探讨其作用机制。方法采用离体血管张力记录法,观察吲哚布芬对大鼠主动脉血管环的作用及不同工具药的影响。结果吲哚布芬（0.3μmol/L、1μmol/L、3μmol/L、10μmol/L和30μmol/L）对KCl（30mmol/L）预收缩的血管环具有浓度依赖性舒张作用,去内皮组舒张作用弱于内皮完整组,说明此舒张作用具有部分内皮依赖性。在KCl预收缩基础上,非特异性NOS抑制剂L-NAME（100μmol/L）处理大鼠胸主动脉后,吲哚布芬的舒张血管作用部分被抑制;加入钾通道阻滞剂4-氨基吡啶4-AP（1mmol/L）、氯化钡BaCl2（1mmol/L）、格列苯脲Gli（10μmol/L）和四乙胺TEA（10mmol/L）,吲哚布芬舒张血管作用均被抑制。结论吲哚布芬具有浓度依赖的舒张血管作用且具有部分内皮依赖性;而其舒血管作用可被反向钠钙交换体阻滞剂KB-R7943增强。吲哚布芬对大鼠胸主动脉的舒张作用可能与KATP通道、Kv通道、KCa通道和KiR通道有关。     

氨氯吡咪对预收缩大鼠胸主动脉血管环的作用及其机制探讨

目的观察氨氯吡咪（AM）对预收缩大鼠胸主动脉血管环的舒张作用并探讨其可能机制。方法采用离体血管环灌流方法,在用KCl（6×10^-2mol／L）或去甲肾上腺素（NE,1×10^-6mol／L）预收缩的去内皮或内皮完整的离体大鼠主动脉环上加入AM,观察其对大鼠主动脉血管环的作用及加入不同工具药后对其舒张血管的影响。结果AM（1×10^-6mol／L-3×10^-5mol／L）对基础状态的大鼠胸主动脉血管环无作用;对KCI（6×10mol／L）和NE（1×10^-6mol／L）预收缩的内皮完整或去内皮的胸主动脉血管环有浓度依赖性的舒张作用,对内皮完整血管环的舒张作用强于去内皮的血管环。一氧化氮合酶抑制剂L—NAME及部分钾离子通道阻断剂四乙胺（TEA,1×10^-2mol／L）、氯化钡（BaCl2,1×10^-3mol／L）预处理对AM诱导的动脉环舒张作用具有明显的抑制效应。结论AM的血管舒张作用具有内皮依赖性,其与内皮NO的合成有关;同时AM可能涉及血管平滑肌细胞的钙激活钾通道和内向整流钾通道的激活。     

杜鹃素对大鼠离体主动脉的舒张作用及机制

目的 探讨杜鹃素(DJS)对大鼠离体主动脉的舒张作用与机制.方法 制备SD大鼠离体主动脉环.采用离体血管环实验方法,通过生物信号采集与分析系统测定血管环的变化.结果 杜鹃素能够浓度依赖性地舒张大鼠离体主动脉环,对KCl预收缩的内皮完整的血管环最大舒张幅度明显强于对去除内皮血管环的舒张作用;预孵一氧化氮合酶抑制剂L-NAME后,DJS对内皮完整的血管环的最大舒张幅度明显降低(P＜0.05或P＜0.001).结论 DJS能够浓度依赖性舒张大鼠离体主动脉,其作用机制可能与血管内皮细胞促进一氧化氮的释放有关.     

大蒜素对大鼠离体肾内动脉血管张力的影响

目的观察大蒜素（Allicin）对离体肾内动脉经血管收缩剂预收缩张力的影响,探讨其对微血管的作用机制。方法显微操作下取SD大鼠肾内动脉,制备成1.8～2.0 mm长的血管条,用两根不锈钢丝穿过血管腔,固定于微血管测定仪的浴槽内,置于37℃通有混合气体（95%O₂+5%CO₂）的生理盐溶液中。平衡1小时后,分别给予受体依赖性血管收缩剂苯肾上腺素（phenylephrine,PE）1μmol·L^-1、5-羟色胺（5-hydroxy tryptamine,5-HT）2μmol·L^-1、血栓素A2类似物U46619 100 nmol·L^-1和非受体依赖性血管收缩剂60mmol·L^-1 KCL预收缩血管,采用累积给药法加入大蒜素,观察不同浓度的大蒜素对血管张力的影响。结果大蒜素对PE、5-HT、U46619预收缩内皮完整的血管环,均呈浓度依赖性的舒张血管作用;对PE预收缩用一氧化氮合酶抑制剂L-NAME(100 mmol·L^-1)孵育30 min保留内皮的血管环以及采用机械法去除内皮的血管环,均呈浓度依赖性的舒张血管作用,与内皮完整组无比较统计学差异;对KCL预收缩内皮完整的血管环,各浓度的大蒜素均无明显的舒张血管作用。结论大蒜素对PE、5-HT、U46619预收缩的血管环具有浓度依赖性舒张作用,对KCL预收缩的血管环无舒张作用。提示其舒张血管的作用与受体途经有关,与L型钙通道途经无关,并且对PE预收缩血管的舒张作用不依赖于内皮功能的完整性。     

大蒜素对大鼠离体肾内动脉血管张力的影响

目的观察大蒜素（Allicin）对离体肾内动脉经血管收缩剂预收缩张力的影响,探讨其对微血管的作用机制。方法显微操作下取SD大鼠肾内动脉,制备成1.8～2.0 mm长的血管条,用两根不锈钢丝穿过血管腔,固定于微血管测定仪的浴槽内,置于37℃通有混合气体（95%O₂+5%CO₂）的生理盐溶液中。平衡1小时后,分别给予受体依赖性血管收缩剂苯肾上腺素（phenylephrine,PE）1μmol·L^-1、5-羟色胺（5-hydroxy tryptamine,5-HT）2μmol·L^-1、血栓素A2类似物U46619 100 nmol·L^-1和非受体依赖性血管收缩剂60mmol·L^-1 KCL预收缩血管,采用累积给药法加入大蒜素,观察不同浓度的大蒜素对血管张力的影响。结果大蒜素对PE、5-HT、U46619预收缩内皮完整的血管环,均呈浓度依赖性的舒张血管作用;对PE预收缩用一氧化氮合酶抑制剂L-NAME(100 mmol·L^-1)孵育30 min保留内皮的血管环以及采用机械法去除内皮的血管环,均呈浓度依赖性的舒张血管作用,与内皮完整组无比较统计学差异;对KCL预收缩内皮完整的血管环,各浓度的大蒜素均无明显的舒张血管作用。结论大蒜素对PE、5-HT、U46619预收缩的血管环具有浓度依赖性舒张作用,对KCL预收缩的血管环无舒张作用。提示其舒张血管的作用与受体途经有关,与L型钙通道途经无关,并且对PE预收缩血管的舒张作用不依赖于内皮功能的完整性。     

利拉鲁肽对离体大鼠胸主动脉环的血管舒张效应及其机制研究

目的：研究利拉鲁肽对离体大鼠胸主动脉环的血管舒张效应及其作用机制。
　　方法：分离32只SD雄性大鼠的胸主动脉环,分成去内皮组（n=16）和内皮完整组（n=16）。采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察利拉鲁肽（1×10-5 mol/L）对去甲肾上腺素（1×10-6 mol/L）预收缩的胸主动脉环的舒张作用。随后内皮完整组又分为左旋硝基精氨酸甲酯干预亚组（n=8）和格列苯脲干预亚组（n=8）,分别接受一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（1×10-4 mol/L）和非特异性ATP敏感性钾通道（KATP）抑制剂格列苯脲（1×10-5 mol/L）的预处理,预处理后利拉鲁肽分别作用于预处理过的去甲肾上腺素预收缩的胸主动脉环,观察利拉鲁肽对离体大鼠胸主动脉环作用的影响。
　　结果：利拉鲁肽对基础状态的胸主动脉环无作用。去甲肾上腺素预收缩胸主动脉环后,当利拉鲁肽浓度达到1×10-5 mol/L时,利拉鲁肽对去内皮组和内皮完整组胸主动脉环均有舒张作用,但对内皮完整组舒张作用更强,胸主动脉环最大舒张幅度达17%（P<0.05）,差异有统计学意义。经左旋硝基精氨酸甲酯和格列苯脲预处理后,左旋硝基精氨酸甲酯干预亚组利拉鲁肽对胸主动脉环舒张幅度为4%（P<0.05）,与预处理前相比差异有统计学意义。格列苯脲干预亚组利拉鲁肽对胸主动脉环舒张幅度为14%（P>0.05）,与预处理前相比差异无统计学意义。
　　结论：利拉鲁肽对去甲肾上腺素预收缩的胸主动脉环有明显的舒张作用,其机制与内皮细胞一氧化氮合酶有关。而KATP未能阻断利拉鲁肽的血管舒张作用。     

Melatonin restores endothelium-dependent relaxation in aortic rings of pancreatectomized rats

In rats turned hyperglycemic by a subtotal pancreatectomy, a decreased relaxation response of aortic rings to acetylcholine (ACh) was found; this effect was amplified by preincubation in a high glucose medium (44 mmol/L). The relaxation response to ACh did not occur in endothelium-denuded rings or after the aortic rings were exposed to l-nitro-arginine methyl ester [L-NAME, a nitric oxide (NO) synthase inhibitor]. Incubation with the NO donor sodium nitroprusside (SNP) restored the impaired relaxation response seen in endothelium-denuded or L-NAME-treated aortic rings. Pancreatectomy decreased the vasorelaxation of aortic rings caused by SNP. Only in pancreatectomized rats, incubation in a high glucose medium impaired the relaxation effect of SNP. To assess whether melatonin preincubation reversed the impaired relaxation response to ACh (intact endothelium aortic rings) or to SNP (endothelium-denuded or L-NAME-treated rings) in hyperglycemic rats, cumulative dose-response curves were performed in the presence of 10(-5) mol/L melatonin. Melatonin preincubation did not modify ACh-induced relaxation of aortic rings in a normal glucose concentration but was highly effective in preventing the impairment of relaxation caused by a high glucose solution. Melatonin was also effective in restoring the impaired SNP-induced vasorelaxation seen in endothelium-denuded or L-NAME-treated aortic rings from hyperglycemic rats. The results further support the improvement by melatonin of the endothelial-mediated relaxation in blood vessels of diabetic rats.     

Abnormal contractile response of aortas from spontaneously hypertensive rats to Ca2+ after depletion of Ca2+ in Ca2+-free medium

Vascular responses of aortic rings from spontaneously hypertensive rats (SHR) were compared to those of the normotensive Wistar-Kyoto rats (WKY) in three sets of experimental protocols. The responses to cumulative doses of KCl indicated that SHR aortic rings were hyperresponsive to low but not high doses of KCl compared to WKY aortic rings. After Ca depletion by prolonged incubation of the rat aortic rings with Ca2+-free, EGTA containing solution, Ca repletion resulted in contraction. The magnitude of such a contraction was dependent on the period of Ca depletion and was highly sensitive to dihydropyridine Ca channel blocker, nifedipine. Although the Ca-depleted aortic rings eventually developed to the same level of maximum tension development upon Ca repletion, it took a considerably shorter period of Ca depletion for SHR than for WKY aortic rings to reach the maximum contraction upon Ca repletion. Our findings support the view that cell membranes of vascular smooth muscle in hypertension are more excitable and more susceptible to membrane destabilization by Ca removal.     

Effect of Red Blood Cells and Hemoglobin on Spontaneously Hypertensive and Normotensive Rat Aortas

Experiments were designed to compare the contractile effect of red blood cells (RBC) on aortic rings with and without endothelium from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Red blood cells of 4 week old WKY and SHR rats induced a negligible increase in tension of aortic rings, either with or without endothelium, being slightly more effective in SHR rats. However, red blood cells of 16 week old rats increased tension of WKY and SHR aortic rings, with endothelium at this age being more pronounced then red blood cells in 4 week old animals. The contractions induced by WKY and SHR red blood cells both in WKY and SHR aortic rings without endothelium at this age are significantly greater compared to the effect on aortic rings with endothelium. Red blood cell ghosts of rats of both strains increased the tension of the rings without endothelium of SHR aorta to near 50% of those induced by red blood cells, whereas they were ineffective in aortic rings without endothelium of WKY rats. Oxyhemoglobin increased the tension of 16 week SHR aortic rings both with and without endothelium, whereas the effect on the rings of WKY rats was negligible. This increase in tension was inhibited by BM 13505, nordihydroguaiaretic acid, and indomethacin in SHR rings both with and without endothelium, demonstrating an eicosanoid involvement in oxyhemoglobin-induced contractions. Hemoglobin or its metabolites may be involved in development or in maintenance of spontaneous hypertensin.     

脉络宁血管舒张作用的实验研究

目的观察脉络宁注射液的血管作用并探讨其可能的机制。方法采用大鼠离体胸主动脉环张力测定法。结果脉络宁注射液能明显舒张由苯肾上腺素(PE)或氯化钾(KCI)预收缩的大鼠主动脉环,其血管舒张作用并不依赖血管内皮。脉络宁注射液对缺氧引起的血管收缩没有抑制作用。对去内皮的血管环,在无钙溶液中,脉络宁注射液能够抑制PE(10-6mol/L)诱导的短暂收缩。TEA敏感性K+通道阻断剂四乙胺(TEA,5×10-3mol/L)可部分抑制脉络宁注射液的舒血管作用。ATP敏感性K+通道阻断剂格列苯脲(Gly,10-3mol/L)并不能抑制脉络宁注射液的舒张血管作用。结论脉络宁注射液的非内皮依赖性血管舒张作用机制可能是通过抑制细胞外钙内流、胞内内质网钙离子释放而起作用。TEA敏感性K+通道的激活部分参与了脉络宁注射液的舒血管作用。ATP敏感性钾通道可能并没有参与。脉络宁注射液不能抑制缺氧引起的血管收缩。     

Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction

To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.     

Pregnancy-induced alterations of relaxation in response to magnesium in the rat aorta may be due to plasma-borne agents

Summary The influence of plasma from pregnant and nonpregnant humans was examined, using magnesium-induced relaxation of precontracted rat aortic rings. The results showing magnesium-induced relaxation of aortic rings from pregnant and nonpregnant rats were compared. In rat aortic rings incubated in plasma from pregnant patients, magnesium was more potent in relaxing the precontractions induced by potassium chloride than in relaxing those induced by phenylephrine. The magnesium-induced relaxation of rings incubated in plasma from normal pregnant subjects was similar to that in unincubated rings from normal pregnant rats. Neither the removal of endothelium nor pretreatment with indomethacin affected the pattern of responses in the rings. The results suggest that the effects of pregnancy on magnesium-induced relaxation of the rat aorta may be mediated by plasma-borne agents, and the mechanisms by which the agents alter the relaxation do not involve either the vascular endothelium or prostaglandin synthesis.     

Effect of melatonin on vascular responses in aortic rings of aging rats

In old animals a marked reduction in endothelium-dependent relaxation occurs. Since there is evidence that the endothelial dysfunction associated with aging may be partly related to the local formation of reactive oxygen species, the purpose of this study was to examine the effect of the natural antioxidant melatonin (10(-5)mol/l) on in vitro contractility of aged aortic rings under conditions of increased oxidative stress (40 m mol/l glucose concentration in medium). Experiments were carried out in 18-20 months old, Wistar male rats, using adult (6-7 months old) animals as controls. A higher plasma lipid peroxidation was found in aged rats as compared to the younger ones. In a first experiment, dose-response curves for acetylcholine-induced relaxation of aortic rings were conducted. Analyzed as a main factor in a factorial ANOVA, age decreased and melatonin augmented the relaxing response to acetylcholine. melatonin's restoring effect on aortic ring relaxation was found in aged aortic rings only and was more pronounced in the presence of a high glucose medium. In a second experiment, the effect of melatonin on the contractility response to phenylephrine of intact or endothelium-denuded aortic rings obtained from aged or control rats was examined in normal or high glucose medium. A main factor analysis in the factorial ANOVA indicated that age and operation augmented, and melatonin decreased, aortic ring contractility response to phenylephrine. Melatonin's restoring effect on aortic contractility was seen in aged aortic rings. The effect of age or a high glucose medium on phenylephrine-induced contractility was more pronounced in the absence of an intact endothelium. Aging did not affect the relaxant response of intact or endothelium-denuded rings to sodium nitroprusside. The results support the improvement by melatonin of vascular response in aging rats, presumably via its antioxidant activity.     

Role of endothelium in the response to endothelin in hypertension

The relation between endothelin and acetylcholine (ACh) was examined and compared in aortas from Wistar-Kyoto (WKY) rats and from stroke-prone spontaneously hypertensive rats (SHRSP). The relaxation produced by ACh in an endothelin-induced contraction was less in aortas from WKY rats than in those from SHRSP. In aortas from WKY rats but not in those from SHRSP, the contraction produced by endothelin was augmented when the intact aortic rings were treated with methylene blue (10(-5) M). This augmentation was also found in preparations of the WKY rat aortic rings in which the endothelium had been removed. The augmentation was not present in SHRSP aortic rings that had been similarly denuded. Treatment with indomethacin (5 x 10(-6) M) had no effect on endothelin-induced contraction in either WKY rat or SHRSP aortic rings. Our findings indicate that endothelin and ACh have in common the ability to release endothelium-derived relaxing factor (EDRF) in WKY rat aortic rings. The reduced endothelium-dependent relaxation in response to ACh in the WKY rat probably reflects the fact that endothelin had already released the EDRF in rings from this strain of rats. The release of EDRF by endothelin is less in SHRSP than it is in WKY rats. Because of this failure of endothelin to release EDRF in SHRSP, endothelin may contribute to the increase in total peripheral resistance in this form of hypertension.     

Decreased vascular contractility induced by hemin is associated with a reduced rho-kinase activity

Objectives

In this study, the role of rho-kinase activity in the modulation of vascular contractility induced by hemin, a heme oxygenase inducer, was investigated.

Methods

Aortic rings from Wistar rats were incubated in physiological saline solution (PSS) containing hemin at 10-4 M for six hours then contracted with phenylephrine, and a dose-response curve was established. The effect of Y-27632, a rho-kinase inhibitor, on the relaxation of the pre-contracted aortic rings was then studied.

Results

Incubation of the aortic rings in hemin induced an increased expression of heme oxygenase 1 (HO-1). A reduction in the contractile force of aortic rings incubated in hemin was observed in response to phenylephrine. Y-27632 at a concentration of 10-6 M induced a 36% relaxation of the control aortic rings but only a 20% relaxation in aortic rings treated with hemin.

Conclusion

These data suggest that the decreased vascular contractility induced by hemin could, in part, result from an inhibition of rho-kinase activity.     

Involvement of Nitric Oxide and Potassium Channels in the Reduction of Basal Tone Produced by Blockade of Thromboxane A2/Prostaglandin H2/ Receptors in Aortic Rings Of Hypertensive Rats

This study was designed to investigate involvement of potassium channels in the action of nitric oxide facilitating reduction of basal tone by thromboxane A₂/prostaglandin H₂receptor blockade with ifetroban in rings of thoracic aorta taken from rats with aortic coarctation-induced hypertension. Ifetroban-induced reduction of basal tone in aortic rings without drug pretreatment was attenuated (P<0.05) in rings pretreated with the nitric oxide synthesis inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 3 × 10<^-4mol/L; 0.55±0.09 g versus 0.23±0.07 g). The vasorelaxing effect of ifetroban also was decreased (P<0.05) in preparations pretreated with a potassium channel blocker, either tetraethylammonium (TEA; 10^-2mol/L) or 4-aminopyridine (4-AP; 3 × 10^-3mol/L). Ifetroban-induced reduction of basal tone was not attenuated in preparations pretreated first with L-NAME and then with sodium nitroprusside (SNP; 6±1 nmol/L) to compensate for the loss of endogenous nitric oxide. However, the facilitatory effect of SNP on ifetroban-induced relaxation of aortic rings pretreated with L-NAME alone was not demonstrable in rings pretreated with L-NAME plus TEA or 4-AP. These observations suggest that a mechanism involving nitric oxide and potassium channels facilitates the reduction in basal tone produced by ifetroban in aortic rings of rats with aortic coarctation-induced hypertension