家兔脑基底动脉离体制备动脉环与张力记录方法的改进及应用价值

为了更好地研究血管药物的作用机制,对家兔脑基底动脉离体制备动脉环和记录张力变化的方法进行了改进。主要有三个方面：①急性放血,从颅顶开颅快速取出脑基底动脉;②在冷光源下,将已离体的脑基底动脉悬浮于预冷灌流液中,再行制备动脉环和进行记录前的各项操作;③利用BL－310微机型生物机能实验系统记录脑基底动脉环在药物作用下的张力变化。结果发现,BL－310微机型生物机能实验系统的精密度、准确度和精确度都比二道重量记录仪高;制备的家兔脑基底动脉环标本在KCI、苯福林和组胺等药物作用下张力变化明显,用BL－310系统能真实地记录到这些张力变化。此结果说明,改进的家兔脑基底动脉离体制备动脉环灌流和记录张力的方法更适用于小动脉生理、病理生理和药理的实验研究。     

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。     

蜂毒肽对大鼠主动脉收缩的作用及与钙内流的关系

为探讨蜂毒肽对心血管系统的作用机理,利用离体大鼠主动脉收缩实验及血管平滑肌细胞＾４５Ｃａ内流定量测定方法,观察了蜂毒肽对血管平滑肌的影响。结果发现：蜂毒肽不影响内皮完整主动脉由苯肾上腺素引起的快速收缩,但可溶度依赖地抑制持续收缩;蜂毒肽对去内皮主动脉环由苯肾上腺素引起的收缩无作用;蜂毒肽对内皮完整主动脉未能产生收缩反应,但可使去内皮动脉环产生收缩和＾４５Ｃａ内流增加,卡手普利和苄普地尔能部分拮抗这     

茶色素胶囊对家兔离体血管平滑肌张力的影响

目的观察茶色素胶囊对离体家兔胸主动脉环舒缩的影响。方法采用测定离体血管环张力的实验方法,观察茶色素胶囊对离体家兔胸主动脉环静息张力的影响以及对去甲肾上腺素或氯化钾（KCl）引起的胸主动脉环收缩的影响。结果不同实验浓度的茶色素对家兔离体胸主动脉环的静息张力无明显作用,与对照组比较无统计学意义（P〉0．05）;2mg／mL。4mg／mL浓度的茶色素对由去甲肾上腺素和KCl引起的胸主动脉环的收缩有一定的抑制作用,与对照组比较差异有统计学意义（P〈0．05）,且高浓度组比低浓度组效果明显。结论茶色素可对抗去甲肾上腺素和KCl等缩血管物质引起的血管收缩,降低血管张力,使血管舒张。     

KB-R7943对大鼠不同器官血管环收缩的影响

目的 研究钠钙交换抑制剂KB-R7943对不同激动剂所致成年大鼠血管收缩的对抗作用或舒张作用及其可能的机制.方法 采用离体血管张力记录方法 ,大鼠动脉环的张力舒缩状态采用PowerLab和DMT系统记录.观察KB-R7943对血管环收缩和舒张的影响以及可能的作用机制.结果 KB-R7943对基础状态的血管环张力没有明显影响;KB-R7943能够浓度依赖性的舒张高钾去极化所致的成年大鼠各器官动脉血管环,对各脏器血管无显著选择性.结论 KB-R7943的血管舒张作用可能与内皮合成并释放NO有关;KB-R7943能够抑制多种致痉剂对肾动脉血管环的收缩作用,对各种致痉剂的对抗作用无选择性.     

低强度红激光局部照射对血管成形术后血管内皮功能的影响

目的　观察低强度红激光照射 (LPRLI)对动脉粥样硬化兔血管成形术后血管内皮修复和功能的影响。方法　新西兰白兔 40只 ,随机分为单纯球囊拉伤组和球囊拉伤并激光照射组各 2 0只 ,建立动脉粥样硬化兔血管损伤模型。激光照射组于球囊拉伤后应用激光球囊导管对损伤血管进行局部照射。对术后第 4周的两组动物 ,固定部位剪取拉伤组和激光照射组损伤的腹主动脉血管 ,采用离体血管功能实验方法 ,观察兔腹主动脉环的张力变化和损伤血管内皮细胞的修复情况。结果　经过LPRLI的兔损伤腹主动脉的内皮依赖性舒张功能明显强于单纯拉伤组血管。右髂动脉损伤段血管损伤面积 ,单纯拉伤组 (6 1 11± 7 12 )mm2 ,激光照射组 (96 71± 8 2 0 )mm2 ,后者的修复面积明显大于前者(P <0 0 1)。结论　LPRLI对动脉粥样硬化兔损伤动脉的内皮依赖性舒张功能具有保护作用并可以促进损伤血管内皮修复     

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。     

Apelin-13对离体大鼠主动脉环舒张作用的实验研究

目的研究新发现的小分子活性肽Apelin-13对离体大鼠主动脉环的舒张作用及其可能的作用途径。方法采用累计加药法,检测Apelin-13对去甲肾上腺素(NE)预收缩的内皮完整的胸主动脉环及去内皮后胸主动脉环张力的变化。结果Apelin-13在10-11~10-7mol.L-1浓度范围内对内皮完整的离体大鼠胸主动脉环具有浓度依赖性的舒张作用,最大舒张率为(44.43±11.1)%,其对内皮完整的血管的舒张作用显著大于去内皮血管(P<0.05),Apelin-13对去内皮的主动脉环的最大舒张率仅为(6.36±2.40)%。结论Apelin-13具有显著的舒张主动脉的作用,其舒张作用依赖于内皮的完整性。     

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。     

Comparison of rabbit coronary arterial relaxation induced by acetylcholine and lemakalim: activation of ATP sensitive potassium channels.

STUDY OBJECTIVE--The purpose was to assess the role of ATP sensitive potassium channels (KATP) in endothelium dependent vasodilatation induced by acetylcholine, or endothelium independent vasodilatation induced by lemakalim in rabbit coronary arteries. DESIGN--The effect of glibenclamide, a specific inhibitor of KATP, on coronary artery relaxation induced by acetylcholine or lemakalim was investigated. The relaxing effectiveness of acetylcholine and lemakalim on coronary arteries precontracted with KCl (K+) or prostaglandin F2 alpha (PGF2 alpha) was compared. EXPERIMENTAL MATERIALS--Left epicardial coronary arteries from male New Zealand white rabbits (2.5-3.0 kg), killed by an overdose of pentobarbitone, were dissected free of connective tissue. Rings suspended in organ baths for the measurement of isometric tension. MEASUREMENTS AND MAIN RESULTS--K+ (30 mmol.litre-1) and PGF2 alpha (3 mumols.litre-1) caused comparable contraction (p greater than 0.05) in endothelium intact or endothelium denuded coronary arterial rings. Acetylcholine induced relaxation was greater in endothelium intact rings precontracted with PGF2 alpha than with K+ and was abolished by the removal of endothelium. Relaxations induced by acetylcholine (0.1 and 0.3 mumol.litre-1) were reduced from 82(SEM 2.7)% and 93(2.8)% to 71(2.4)% and 82(2.7)% (p less than 0.05), and to 63(3.2)% and 79(4.5)% (p less than 0.05 or less than 0.01) by glibenclamide (3 and 10 mumols.litre-1) respectively in PGF2 alpha precontracted rings; and also attenuated (p less than 0.05 or less than 0.01) in K+ precontracted rings. Lemakalim induced relaxation was greater in endothelium denuded rings precontracted with PGF2 alpha than with K+, and was markedly reduced by glibenclamide (p less than 0.01). CONCLUSIONS--These results suggest that activation of KATP may partially be involved in endothelium dependent relaxation induced by acetylcholine in rabbit coronary arteries. Lemakalim-induced endothelium independent relaxation results mainly from activation of KATP.     

Actions of prostaglandin I2 and thromboxane A2 on vascular smooth muscle tissues

Actions of prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) on vascular smooth muscles were investigated in relation to the function of the endothelium. In intact vascular smooth muscle tissues of the thoracic aorta, PGI2-Na, used as a substitute substrate of PGI2, relaxed the precontracted tissue, in a dose dependent manner, in intact tissues and also after mechanical ablation of the endothelium. Acetylcholine (ACh) relaxed the tissue precontracted by noradrenaline, in the presence or absence of indomethacin; however, the relaxation required the presence of an intact endothelium. On the other hand, increased amounts of PGI2 with the application of acetylcholine, as estimated from the amount of 6-keto-PGF1 alpha, were markedly attenuated by indomethacin. In smooth muscles of this tissue without the endothelium, ACh synthesized lesser amounts of PGI2, while PGI2-Na increased the amount of cyclic AMP. Thus, PGI2 was synthesized in both the endothelium and smooth muscles. The former produces a larger amount of PGI2 than the latter, but the PGI2 synthesized in smooth muscles may act more potently on the smooth muscle than does that synthesized in the endothelium. In the canine coronary artery, mechanical responses induced by TXA2, as estimated from actions of 9, 11,-epithio-11, 12-methano-thromboxane A2 (STA2) were enhanced after ablation of the endothelium. The minimum concentration of STA2 required to produce the contraction was above 1 nM and the maximum amplitude was evoked with 30 nM. The amplitude of the STA2-induced contraction was reduced in Ca-free solution or with the application of nifedipine. However, prazosin, propranolol or atropine had no effect on the STA2-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

ATP produces vasodilation via P1 purinoceptors and vasoconstriction via P2 purinoceptors in the isolated rabbit central ear artery

P1 and P2 purinoceptors mediating mechanical responses in isolated rabbit ear artery were studied by comparing responses to adenosine triphosphate (ATP), alpha, beta-methylene ATP, and adenosine, both when endothelial cells were intact and when they had been removed by mechanical rubbing (as confirmed by histochemical staining and near abolition of relaxation to acetylcholine). alpha, beta-Methylene ATP and ATP (but not adenosine or acetylcholine) contracted preparations at resting tone. alpha, beta-Methylene ATP was significantly more potent as a contractile agent than ATP. Neither was significantly affected by removal of the endothelium. Acetylcholine, ATP, and adenosine relaxed arteries whose tone had been raised by 10(-6) M histamine. Removal of the endothelium virtually abolished relaxations to acetylcholine and significantly decreased those to adenosine and ATP. All relaxations to adenosine and ATP were significantly antagonised by 8-phenyltheophylline, a potent P1 purinoceptor antagonist. alpha, beta-Methylene ATP further contracted the high-tone preparation and was again unaffected by removal of the endothelium. These results confirm that endothelial cells can mediate vasodilation. They also show that adenosine (and ATP) can elicit vasodilation via P1 purinoceptors both on the endothelial cells and on the smooth muscle of the isolated rabbit central ear artery. P2 purinoceptors, however, appear to be located on the smooth muscle only and mediate vasoconstriction.     

Electrical responses of smooth muscle cells during cholinergic vasodilation in the rabbit saphenous artery

Isolated smooth muscle tissues of the rabbit saphenous artery precontracted with norepinephrine (NE) were relaxed by acetylcholine (ACh, greater than 10(-7) M) or oxotremorine (greater than 10(-7) M), through the activation of muscarinic receptors, only when the endothelial cells were intact. ACh (greater than 10(-7) M) transiently hyperpolarized the membrane (1-4 minutes) with an associated decrease in the membrane resistance, either in the presence or absence of NE, and these changes ceased during the continuous application of ACh. The ACh-induced transient hyperpolarization was not generated after mechanically removing the endothelium or by treatment with atropine. Oxotremorine (up to 10(-5) M) did not alter the membrane potential in the presence or absence of the endothelium. NE (10(-6) M) depolarized the smooth muscle membrane, which remained unchanged by additional application of ACh or oxotremorine for more than 5 minutes, or after removal of the endothelium. The excitatory junction potential generated by perivascular nerve stimulation was inhibited by ACh (greater than 10(-9) M) or oxotremorine (greater than 10(-9) M) in a concentration-dependent manner. These inhibitory actions of ACh or oxotremorine were blocked by atropine but were not affected by removal of the endothelial cells. These results suggest that the inhibitory actions of muscarinic agonists on electrical responses of smooth muscle cells of the rabbit saphenous artery were mainly indirect, i.e., a release of inhibitory substances from the endothelial cells and the inhibition of adrenergic transmission. The former required higher concentrations of ACh or oxotremorine, thereby suggesting that the latter may be more important for vasodilation related to cholinergic mechanisms.     

Development of a large fibromuscular intimal thickening does not impair endothelium-dependent relaxation in the rabbit carotid artery

The release of endothelium-derived relaxing factor (EDRF) was examined in the rabbit carotid artery 6 weeks after denudation with an inflated balloon catheter in vivo. A concentric, fibromuscular intimal thickening of variable width developed in all areas lined with either regenerated endothelium or modified luminal smooth muscle cells. In vitro studies showed that in vessels precontracted with serotonin, only the re-endothelialized areas could relax to the endothelium-dependent dilators methacholine, substance P and the Ca2+ ionophore A23187. Re-endothelialized areas with large concentric, fibromuscular intimal thickening (between 10 and 20 cells thick) relaxed with a similar sensitivity and maximum to methacholine compared with control areas. It is concluded that newly generated endothelial cells release EDRF whilst the specialized lining smooth muscle cells present 6 weeks after injury do not, and that the presence of a large fibromuscular intima does not prevent EDRF from reaching the media to cause relaxation.     

Acetylcholine and adenosine diphosphate cause endothelium-dependent relaxation of isolated human pulmonary arteries

Endothelium-dependent vasorelaxation mediated by endothelium-derived relaxing factors (EDRF) has been extensively studied in animals but only limited studies in man are available. Demonstration of EDRF-mediated dilatation of human vessels is fundamental for understanding the mechanisms of vascular diseases in man. We have investigated endothelium-dependent relaxation of isolated human pulmonary arteries. Vascular segments, taken from uninvolved regions of resected lung from eight patients undergoing lobectomy for lung carcinoma, were cut into rings. In rings precontracted with phenylephrine, both acetylcholine (ACh) and adenosine diphosphate (ADP) induced dose-dependent relaxation in the presence of endothelium but not when the endothelium had been carefully removed. The rings without endothelium relaxed completely with sodium nitroprusside, a vasodilator agent acting directly on vascular smooth muscle. Pre-incubation with indomethacin, a cyclo-oxygenase inhibitor which blocks production of prostacyclin, did not alter the vasorelaxant responses to ACh and ADP, suggesting that one (or several) non-prostanoid EDRF(s) are responsible for the endothelium-dependent relaxation of isolated human pulmonary arteries.     

Effects on the rabbit coronary artery of LP-805, a new type of releaser of endothelium-derived relaxing factor and a K+ channel opener.

In the rabbit epicardial coronary artery, 8-tert-butyl-6,7-dihydropyrolo[3,2-e]5-methylpyrazolo [1,5-a]pyrimidine-3-carbonitrile (LP-805, greater than 0.1 microM) hyperpolarized the muscle membrane in both proximal (diameter, 1-1.2 mm) and distal (diameter, 0.1-0.2 mm) regions of intact (+E) tissue, in which endothelium is present, and endothelium-denuded (-E) tissue. LP-805-induced hyperpolarization was inhibited by glibenclamide. In -E tissues in both regions, acetylcholine (ACh, greater than 0.1 microM) depolarized the membrane, and LP-805 inhibited the depolarization. However, in +E tissues, ACh (greater than 0.1 microM) transiently hyperpolarized the membrane that was not modified by glibenclamide (10 microM), charybdotoxin (100 nM), and NG-nitro-L-arginine (L-NNA, 100 microM). In -E tissues of both regions, LP-805 consistently inhibited the 10 microM ACh-induced contraction (IC50, 2.8 microM), and 10 microM glibenclamide shifted this concentration-response curve to the right (IC50, 20 microM). In +E tissues, LP-805 more potently inhibited the ACh-induced contraction (IC50, 0.3 microM), and this inhibition was prevented by L-NNA (100 microM) but not by indomethacin or glibenclamide (10 microM). In -E and +E tissues of both regions, LP-805 repolarized the high K(+)-induced depolarization (less than 20 mM) and relaxed the tissues precontracted by high K+ (less than 30 mM); these electrical and mechanical effects of LP-805 were prevented by glibenclamide (10 microM) in +E tissues. In +E tissues, the K(+)-induced contraction (less than 30 mM) was more strongly inhibited than in -E tissues, but after treatment with L-NNA, LP-805 relaxed -E and +E tissues precontracted to the same extent in the presence of high K+. LP-805 (10 microM) did not inhibit the Ca(2+)-induced contraction in skinned muscle tissues but did slightly inhibit the ACh-induced contraction in Ca(2+)-free solution containing 2 mM EGTA. Thus, LP-805 has a potent releasing action on endothelium-derived relaxing factor and also the potential to open the glibenclamide-sensitive K+ channel. These events would account for the dilation of the rabbit coronary artery exposed to LP-805.     

Effects of lysophosphatidylcholine and palmitylcarnitine — lipid metabolites produced in ischemia — on porcine coronary and rabbit femoral arteries

Summary In organ bath experiments, amphiphilic lipids lysophosphatidylcholine (LPC) and palmitylcarnitine (PLC) produced a small increase in tension of nonprecontracted strips of porcine coronary artery with a subsequent decrease to initial level after high concentrations of the agents, both in intact and endothelium-denuded preparations. Both amphiphiles produced dose-dependent but incomplete relaxation of intact coronary strips precontracted with high potassium. The effect of PLC was more pronounced. LPC, 3 · 10⁻⁶ mol · l⁻¹, did not influence Ca⁺⁺-dose-response relationships, while PLC in concentration of 10⁻⁵ mol · l⁻¹ abolished the decline in the second Ca⁺⁺-dose-response curve. Neither PLC nor LPC in concentrations of 3 · 10⁻⁶ mol · l⁻¹ influenced endothelium-dependent relaxation produced by bradykinin precontracted with high potassium porcine coronary artery. Both amphiphiles did not change tension of nonprecontracted and precontracted with phenylephrine, 10⁻⁶ mol · l⁻¹, rabbit femoral artery ring segments or Ca⁺⁺-dose-response relationships with and without endothelium.     

Action of fenoldopam, a selective dopamine (DA1) receptor agonist, on isolated human arteries

The effects of a DA1 dopamine receptor selective agonist, fenoldopam, were examined on human blood vessels. Fenoldopam relaxed precontracted human arteries in vitro from brachial, cerebral, cervical, colic, coronary, lumbar, pulmonary, renal and splenic sites. Fenoldopam failed to relax uterine or external iliac arteries or saphenous vein segments. These effects of fenoldopam were not endothelium dependent, but were antagonised by the selective DA1 receptor antagonists, SCH 23390, (+)-butaclamol, and (R)- more than (S)-sulpiride. The effect of fenoldopam may involve cyclic adenosine monophosphate. These studies indicate the presence of DA1 receptors on a variety of large isolated human arteries.