胰岛素对数种缩血管物质作用的影响

目的 观察胰岛素对去甲肾上腺素、内皮素－1、氯化钾（KCl)、血管紧张素Ⅱ和5－羟色胺缩血管作用的影响。方法 用SD大鼠的离体动脉血管观察缩血管物质的作用。结果 在含有1mU/ml胰岛素环境中，胰岛素对数种缩血管作用机制不同的物质有程度不同的血管增敏作用。对去甲肾上腺素、内皮素－1和KCl有明显的增敏效果；对血管紧张素Ⅱ有增敏趋势，但无显性差异；对5－羟色胺无增敏效应。结论 胰岛素在高血压的发病过程中可能起重要作用。     

阿托品对6种血管活性物质收缩犬离体脾动脉作用的影响

应用血管插管法观察了阿托品１μｍｏｌ·Ｌ－１对数种血管收缩物质作用的影响。去甲肾上腺素、去氧肾上腺素、５－羟色胺、组织胺、三磷酸腺苷（ＡＴＰ）及氯化钾（ＫＣｌ）可以收缩犬离体脾动脉标本，它们的收缩血管作用呈量效关系。应用１μｍｏｌ·Ｌ－１阿托品灌流脾动脉标本时，５－羟色胺、ＡＴＰ及ＫＣｌ的缩血管效应无显著变化，但是去甲肾上腺素、去氧肾上腺素及组织胺的收缩血管活性显著降低。以上结果表明，在犬离体脾动脉标本，１μｍｏｌ·Ｌ－１浓度阿托品具有抑制α肾上腺素受体激动剂及组织胺的收缩血管作用。     

异紫堇啡碱对血管平滑肌钙内流和钙释放的影响

目的研究异紫堇啡碱（ＩＳＯＣ）对血管平滑肌钙内流和钙释放的影响，以初步阐明其作用方式。方法利用兔胸主动脉螺旋条标本观察ＩＳＯＣ对去甲肾上腺素（ＮＡ）及ＫＣｌ量效曲线的影响和对无钙液中ＮＡ、ＣａＣｌ２复钙、咖啡因缩血管效应的影响。结果ＩＳＯＣ１０μｍｏｌ·Ｌ－１对ＮＡ的量效曲线呈非竞争性拮抗作用，而对高钾的作用则不明显。在无钙液中，ＩＳＯＣ１００μｍｏｌ·Ｌ－１能明显抑制ＮＡ所致的收缩及复钙后外钙内流诱发的收缩，ＩＳＯＣ１０及３０μｍｏｌ·Ｌ－１则只作用于前者；各实验浓度的ＩＳＯＣ对咖啡因在无钙液中的缩血管作用均无影响。结论ＩＳＯＣ抑制受体中介的钙释放和钙内流，但不是典型的钙拮抗剂。     

左旋千金藤定碱对培养牛主动脉血管平滑肌细胞胞内游离Ca~(2+)的影响

目的：研究左旋千金藤定碱（ｌ－ｓｔｅｐｈｏｌｉｄｉｎｅ，ＳＰＤ）对血管平滑肌的作用。方法：采用Ｆｕｒａ－２和ＡＲ－ＣＭ－ＭＩＣ阳离子测定系统测定培养牛主动脉血管平滑肌细胞内游离钙。结果：ＳＰＤ１～１００μｍｏｌ·Ｌ－１不影响静息［Ｃａ２＋］ｉ，但可剂量依赖地抑制高Ｋ＋引起的［Ｃａ２＋］ｉ增高，其ＩＣ５０为３９．６（９５％可信限２３．４～６７．１）μｍｏｌ·Ｌ－１，但其作用弱于尼群地平；ＳＰＤ１～１００μｍｏｌ·Ｌ－１对去甲肾上腺素、血管紧张素Ⅱ、５－ＨＴ、ＡＴＰ引起的［Ｃａ２＋］ｉ增高也有明显的抑制作用；高浓度ＳＰＤ对无外钙时去甲肾上腺素引起的［Ｃａ２＋］ｉ增高也有一定的抑制作用。结论：左旋千金藤定碱对培养血管平滑肌细胞电压依赖性钙通道和受体调控性钙通道均有抑制作用；其对电压依赖性钙通道的抑制作用弱于尼群地平。     

内皮素及其受体拮抗剂的研究进展

198 8年 ,日本学者Yanagisawa等[1] 首次从培养的猪主动脉内皮细胞上层清液中分离得到一族生物活性多肽 ,命名为内皮素 (endothelin ,ET)。它具有强大的缩血管和促进血管平滑肌细胞增生的作用 ,内皮素的缩血管作用仅次于尿紧张素Ⅱ(urotensinⅡ ,迄今为止发现的最强的缩血管物质 ) ,其效价比血管紧张素Ⅱ、加压素、去甲肾上腺素约高一个数量级。同时 ,内皮素也是一种内源性损伤因子 ,在心、脑、肺、肾和血管等多种疾病的发病中都具有重要意义 ,是继心钠素之后 ,心血管活性多肽和内分泌研究的又一个“热点” ,随着内皮素的分子生物学、生物…     

吡那地尔对高血压血管重构的影响

与同月龄同品系正常血压大鼠相比，自发性高血压大鼠（ＳＨＲ）主动脉对去甲肾上腺素（ＮＥ）和ＫＣｌ缩血管的反应降低；主动脉以ＫＣｌ预收缩后，乙酰胆碱（ＡＣｈ）和硝普钠（ＳＮＰ）舒血管作用无显著变化；以ＮＥ预收缩后，ＡＣｈ舒血管作用也无显著性变化，但ＳＮＰ舒血管作用显著减弱．ＳＨＲ经吡那地尔（Ｐｉｎ，２ｍｇｋｇ－１ｄ－１，３０ｄ）治疗后，和赖诺普利（Ｌｉｓ，１２ｍｇｋｇ－１ｄ－１，３０ｄ）治疗后的作用相似，可逆转主动脉对ＮＥ缩血管反应降低，但不改善主动脉对ＫＣｌ缩血管反应降低；可逆转ＮＥ预收缩主动脉后ＳＮＰ舒血管作用的降低．另一方面，Ｐｉｎ也可逆转高血压时肠系膜动脉和主动脉的中层壁增厚及中层壁厚与内径比例增大．表明Ｐｉｎ与Ｌｉｓ的治疗作用有相似之处，可逆转高血压血管结构和功能重构．     

内皮素受体拮抗剂及其对心脑血管疾病的治疗作用

<正>1988年,Yanagisawa及其同事从培养的猪的主动脉内皮细胞上清液中提取纯化出一种含有21个氨基酸,具有强大缩血管和促血管平滑肌细胞增殖的小分子肽,命名为内皮素-1(Endothelin,ET-1)。内皮素作为一族生物活性多肽,是迄今为止发现的最强的缩血管物质之一,其效价比血管紧张素Ⅱ、加压素、去甲肾上腺素约高一个数量级,内皮素在许多     

Effects of Tetrandrine on Cytosolic Free Calcium in Cultured Bovine Aortic Smooth Muscle Cells

利用Ｆｕｒａ２技术和ＡＲＣＭＭＩＣ阳离子系统研究了粉防己碱对传代培养牛主动脉血管平滑肌细胞内游离钙的影响。粉防己碱（１～１００μｍｏｌ·Ｌ－１）不影响血管平滑肌细胞的静息钙，但在有胞外钙存在时，对高钾，５羟色胺，ＡＴＰ，血管紧张素Ｉ，去甲肾上腺素引起的胞内钙升高有抑制作用；在无胞外钙存在时，粉防己碱对苯肾上腺素引起的胞内钙升高也有一定的抑制作用。粉防己碱对高钾升高内钙的抑制作用呈剂量依赖性，ＩＣ５０值为９．２（９５％可信限：５．７～１４．９）μｍｏｌ·Ｌ－１。上述结果提示粉防己碱对血管平滑肌细胞的电压依赖性钙通道和受体调控性钙通道均有阻滞作用，对受体调控性钙通道阻滞作用主要表现为阻滞钙离子内流。     

替米沙坦对慢性心力衰竭患者神经内分泌激素的影响

目的 探讨替米沙坦对慢性心力衰竭患者神经内分泌激素的影响.方法 将96例慢性心力衰竭患者(心功能Ⅱ～Ⅳ级)随机分为两组,分别接受替米沙坦、贝那普利治疗.放射免疫法测定治疗前、治疗3个月后血浆去甲肾上腺素、肾素、血管紧张素Ⅱ、醛固酮及内皮素水平的变化.结果 替米沙坦、贝那普利治疗后血浆去甲肾上腺素、内皮素水平均有明显下降(P＜0.01);贝那普利组血浆肾素、血管紧张素Ⅱ、醛固酮水平无显著变化(P＞0.0 5);替米沙坦组血浆肾素、血管紧张素Ⅱ水平有显著下降(P＜0.01),但醛固酮水平无明显变化(P＞0.0 5).结论 替米沙坦对慢性心力衰竭患者神经内分泌激素只有部分改善作用.     

治疗吗啡依赖和戒断的有效药物

除了阿片受体系统以外，神经递质去甲肾上腺素、多巴胺、乙酰胆碱、兴奋性氨基酸以及它们偶联的受体信息传导系统，还有５－羟色胺，γ－氨基丁酸以及大脑内具有抗阿片肽作用的多肽包括胆囊收缩素、胰高血糖素、血管紧张素Ⅱ、生长抑素和催产素，或多或少地参与了吗啡依赖...     

Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits

1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo-oxygenase pathway, underlies the diversity of responses of regional kidney perfusion to vasoactive agents, we tested the effects of intravenous indomethacin on responses to renal arterial bolus doses of vasoactive agents in pentobarbitone-anaesthetized rabbits. 2. Total renal blood flow (RBF) and regional kidney perfusion were determined by transit time ultrasound flowmetry and laser-Doppler flowmetry, respectively. 3. Responses of regional kidney blood flow to vasoactive agents were diverse: noradrenaline reduced cortical but not medullary perfusion, [Phe 2,Ile 3,Orn 8]-vasopressin reduced medullary perfusion more than cortical perfusion, endothelin-1 and angiotensin II increased medullary perfusion in the face of reduced cortical perfusion, while acetylcholine, bradykinin and the nitric oxide donor methylamine hexamethylene methylamine (MAHMA) NONOate all increased both cortical and medullary perfusion. 4. Indomethacin administration was followed by reductions in total RBF (17 +/- 6%), cortical perfusion (13 +/- 5%) and medullary perfusion (40 +/- 8%). Angiotensin II- and endothelin-1-induced increases in medullary perfusion were abolished by indomethacin, but indomethacin had no significant effects on responses of regional kidney perfusion to acetylcholine, bradykinin, MAHMA NONOate, noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin. 5. Our results suggest that vasodilator cyclo-oxygenase products contribute to the maintenance of resting renal vascular tone, particularly in vascular elements controlling medullary perfusion. Cyclo-oxygenase products also appear to mediate endothelin-1- and angiotensin II-induced increases in medullary perfusion. However, regionally specific engagement of cyclo-oxygenase-dependent arachidonic acid metabolism does not appear to contribute to the differential effects of noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin on cortical and medullary perfusion.     

Comparative studies of the angiogenic activity of vasoactive intestinal peptide, endothelins-1 and -3 and angiotensin II in a rat sponge model.

1 The angiogenic activity of four vasoactive peptides with a range of vasodilator and vasoconstrictor properties, i.e. vasoactive intestinal peptide (VIP), endothelin-1, endothelin-3 and angiotensin II, were investigated in a rat sponge model. Neovascularization was assessed by the 133Xe clearance technique and confirmed by histological studies. 2 Daily doses of the vasodilator peptide, VIP (1000 pmol), caused intense neovascularization, but a lower dose (10 pmol) produced no apparent effect. However, the lower dose of VIP, when given with a subthreshold dose of interleukin-1 alpha (0.3 pmol), produced an angiogenic response similar to that seen with the higher dose of VIP. The neovascular response induced by co-administration of VIP and interleukin-1 alpha was inhibited by simultaneous administration of 100 pmol VIP (10-28), a specific VIP receptor antagonist. 3 In contrast, daily doses of 10, 100 or 1000 pmol endothelin-3 (a mixed vasoconstrictor and vasodilator with more marked vasodilator activity) or of 100 or 1000 pmol endothelin-1 (also with mixed activity but with much more pronounced vasoconstrictor response) produced no apparent effect on sponge-induced angiogenesis. 4 The vasoconstrictor peptide, angiotensin II, in daily doses of 1000 pmol, caused an intense neovascularization like VIP but lower doses of angiotensin II (10 or 100 pmol) produced no apparent effect. The lowest dose of angiotensin II (10 pmol) when administered with the subthreshold dose of interleukin-1 alpha (0.3 pmol) had no effect on the basal neovascular response in the sponges. The angiotensin II-induced neovascular response was inhibited by co-administration of 100 nmol of the specific AT1 receptor antagonist, losartan, but not by the AT2 receptor antagonist, PD 123319. 5 These data show that VIP and angiotensin II possess angiogenic activity. However, endothelin-1 and endothelin-3 had no activity at the doses used. Thus the angiogenic response is not related to local vasoconstriction or vasodilatation in the sponges. The blockade of VIP- and angiotensin II-induced angiogenesis at the receptor level suggests that receptor modulation could provide a strategy for the management of angiogenic diseases.     

FACILITATION OF NORADRENALINE RELEASE BY ISOPRENALINE IN RAT ISOLATED ATRIA DOES NOT INVOLVE ANGIOTENSIN II FORMATION

1. Rat isolated atria were incubated with 3H-noradrenaline and the intramural sympathetic nerves were stimulated at 2 Hz for 60 s. The stimulation-induced (SI) efflux of radioactivity was used as an index of release of transmitter noradrenaline. 2. Isoprenaline (0.1 mumol/L) alone did not increase noradrenaline release. Cocaine (30 mumol/L) produced a 73% increase in the stimulation-induced release of noradrenaline. In the presence of cocaine, isoprenaline enhanced noradrenaline release by 22%. 3. In the presence of cocaine, both angiotensin I (0.3 mumol/L) and angiotensin II (0.3 mumol/L) produced almost two-fold enhancements in the SI release of noradrenaline. 4. Captopril (5 mumol/L) blocked the facilitatory effect of angiotensin I on noradrenaline release but did not alter that of isoprenaline. 5. Saralasin (0.1 mumol/L) reduced the facilitatory effect of angiotensin II on noradrenaline release but did not alter that of isoprenaline. 6. The findings indicate that the facilitation of noradrenaline release by isoprenaline in rat atria is not mediated by local formation of angiotensin II.     

The effect of angiotensin II and noradrenaline alone and in combination on renal sodium excretion in man.

1. The renin-angiotensin-aldosterone-system is important for the maintenance of sodium balance in man. Recent animal evidence suggests the angiotensin II can modulate the effect of the renal sympathetic nervous system on renal function. We have investigated the possible interaction of physiological doses of angiotensin II and noradrenaline on sodium excretion in man. 2. Seven normal volunteers were studied on four occasions during maximum water diuresis sustained by oral hydration. Samples were obtained during a baseline and four subsequent 20 min periods (A-E). Placebo or noradrenaline was infused over periods B-E, and angiotensin II infused over period C. 3. There was no change in systemic blood pressure, heart rate or creatinine clearance caused by infusion of either angiotensin II, noradrenaline or both in combination. 4. Noradrenaline alone caused a significant fall in absolute and fractional sodium excretion. Angiotensin II when infused with placebo caused a 37% fall in absolute sodium excretion and a 32% fall when infused with noradrenaline (no significant difference between the 2 days). Similar changes were seen for urinary flow and fractional sodium excretion. 5. We have therefore found no evidence to support a postsynaptic interaction of low doses of angiotensin II and noradrenaline on renal sodium excretion in man.     

The effect of angiotensin II on endogenous noradrenaline release in man.

1. Considerable data from animal studies suggest that angiotensin II exerts a facilitatory effect on noradrenaline release. We sought evidence for such an effect in man by examining how a subpressor dose of angiotensin II (1.5 ng kg-1 min-1) influences the haemodynamic and plasma noradrenaline responses to physiological stimulation of the sympathetic nervous system. 2. The physiological stimuli investigated were a cold pressor test, the response to standing from lying, bicycle exercise and forearm isometric exercise. 3. The presence of the angiotensin II infusion had no effect on the systolic blood pressure, diastolic blood pressure, heart rate or plasma noradrenaline responses to stimulation of the sympathetic nervous system. 4. We have therefore found no evidence to support the enhancement of noradrenaline release by this low dose of angiotensin II in man.     

Modulation of noradrenaline release in the pithed rabbit: a role for angiotensin II

This study in the pithed rabbit with electrically stimulated sympathetic outflow (spinal region, T-8; 3 Hz) was conducted to determine the contribution of the renin-angiotensin system to noradrenaline release in vivo. The rate of noradrenaline release (spillover) into the plasma was determined from the endogenous plasma noradrenaline level and the simultaneously determined noradrenaline plasma clearance. In the pithed rabbit, infusion of angiotensin II (0.1 microgram/kg/min i.v.) failed to increase the noradrenaline release rate and only slightly increased blood pressure. On the other hand, the angiotensin-converting enzyme inhibitor captopril (1 mg/kg i.v.) decreased both blood pressure and the noradrenaline release rate. Bilateral nephrectomy was performed to reduce endogenous angiotensin II formation; and in this case, infusion of angiotensin II markedly increased the noradrenaline release rate and blood pressure, whereas captopril had no effect on either parameter. These results suggest that angiotensin II modulates noradrenaline release in vivo through activation of facilitatory prejunctional angiotensin II receptors, and that in the pithed rabbit these receptors are probably maximally activated by endogenously synthesized angiotensin II. The actions of angiotensin II on noradrenaline release open the possibility that increases in blood pressure in the pithed rabbit--by decreasing renin release via intrarenal baroreceptors and hence decreasing angiotensin II formation--may lead to decreased noradrenaline release. This was investigated using phenylephrine (6 micrograms/kg/min i.v.), a selective alpha 1-adrenoceptor agonist, and adrenaline (1 microgram/kg/min i.v.), and alpha 1/alpha 2-agonist. Both drugs increased blood pressure and decreased the noradrenaline release rate. After bilateral nephrectomy, the inhibitory effect of phenylephrine on noradrenaline release was abolished, whereas that of adrenaline was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of prostaglandin synthesis does not affect contractile responses to noradrenaline,serotonin, angiotensin II nor endothelin-1 in human forearm isolated veins

1. The functional role of endogenous cyclo-oxygenase products was examined in the human forearm isolated vein. 2. Six healthy normal adult males (age > 18 years old) were recruited. Forearm veins were biopsied and ring segments mounted in standard organ baths for recording of isometric force. 3. Noradrenaline (-log molar EC50: 7.75 +/- 0.19; -log molar threshold concentration: 8.80 +/- 0.20), 5-hydroxytryptamine (-log molar EC50: 7.52 +/- 0.17; -log molar threshold concentration: 9.50 +/- 0.64), angiotensin II (-log molar threshold concentration: 9.00 +/- 0.28) and endothelin-1 (-log molar threshold concentration: 9.13 +/- 0.47) were equipotent in this preparation. Indomethacin (10 microM) had no effect on either the threshold concentration or EC50 of noradrenaline, 5-hydroxytryptamine nor the threshold concentration of angiotensin II nor endothelin-1. 4. Sodium nitroprusside (1 nM-10 microM) relaxed noradrenaline-precontracted preparations. Evidence of minimal endothelial influence was confirmed by the lack of relaxant response to acetylcholine (1 nM-10 microM). Histology using silver staining confirmed that endothelial cells were absent over greater than 90% of the lumen surface. 5. We conclude that endogenous prostanoids derived from smooth muscle cells, either released basally or agonist-stimulated, do not play a role in the regulation of vascular tone in the human forearm isolated vein.     

Vascular hyporeactivity to angiotensin II and noradrenaline in a rabbit model of obesity

This study was conducted to explore the vascular reactivity of angiotensin II and noradrenaline and their relationship with endothelial function in rabbits fed a high-fat diet (HFD). The animals were fed either an HFD or regular chow [control diet (CD)]. After 12 weeks, the rabbits fed the HFD showed higher blood pressure, body weight, and insulin levels. Glucose tolerance was impaired and positively related to blood pressure. An endothelium-independent decrease of the sensitivity to angiotensin II [pD2 endothelium-intact aortic rings (E+) in CD: 8.02 ± 0.07 vs. HFD: 7.60 ± 0.01; pD2 endothelium-removed aortic rings (E-) in CD: 8.16 ± 0.11 vs. HFD: 7.83 ± 0.16] and noradrenaline (pD2 E+ in CD: 6.36 ± 0.06 vs. HFD: 5.29 ± 0.06; pD2 E- in CD: 6.11 ± 0.08 vs. HFD: 5.80 ± 0.08) was found. Noradrenaline desensitized the angiotensin II response (pD2 with noradrenaline pretreatment in E+: 7.03 ± 0.16; in E-: 7.10 ± 0.02), but angiotensin II did not change the noradrenaline response. Acetylcholine maximal relaxation and basal nitric oxide (NO) release were comparable in both diet groups. The efficacy of angiotensin II (Rmax CD: 4604 ± 574 mg vs. HFD: 3251 ± 533 mg) and noradrenaline (Rmax CD: 11,675 ± 804 mg vs. HFD: 7975 ± 960 mg) was reduced in E+. L-N-nitroarginine methyl ester (L-NAME) recovered the efficacy of noradrenaline (Rmax L-NAME: 12,015 ± 317 mg). In contrast, L-NAME had no effect on the angiotensin II response. Noradrenaline enhanced NO levels, but angiotensin II did not. Therefore, NO was associated with hyporeactivity to noradrenaline. The resting potential was more negative in E+, and the endothelium diminished the angiotensin II-induced depolarization. These findings demonstrated that the crosstalk and the endothelium may induce hyporeactivity to angiotensin II and noradrenaline as a mechanism to compensate the increase in the blood pressure in HFD-induced obesity.     

Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs.

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of vasoconstriction by frusemide in the rat.

Mesenteric blood flow was measured in anaesthetized rats with a non-cannulating electromagnetic flow probe around the superior mesenteric artery. Reductions in blood flow were produced by intravenous bolus injections of angiotensin II (1-300 ng) and noradrenaline (3-300 ng) before and after the administration of frusemide (5 mg kg-1, i.v.). Loss of volume after frusemide was prevented by either a urinary bladder-intravenous shunt or replacement of urinary output by intravenous saline. Frusemide administration caused a small increase in baseline blood pressure of 3.2 +/- 1.3 mmHg (P less than 0.05) but did not change mesenteric blood flow. This dose of frusemide inhibited the vasoconstrictor responses to both angiotensin II and noradrenaline (P less than 0.01, two way analysis of variance). Responses to angiotensin II were inhibited to a greater extent. Acute bilateral nephrectomy or treatment with indomethacin (2 mg kg-1, i.v.) completely prevented the inhibitory effect of frusemide on the responses to angiotensin II and noradrenaline. To test whether frusemide-induced increased endogenous levels of angiotensin II may be responsible for the effects of frusemide on the vasoconstrictor responses, a separate group of rats were not given frusemide but were infused with exogenous angiotensin II (12.5-25 ng kg-1 min-1). This produced a small increase in mean blood pressure (4.0 +/- 1.4 mmHg, P less than 0.05) but did not change baseline mesenteric blood flow. Unlike frusemide, the responses to bolus injections of angiotensin II and noradrenaline were not changed by the infusion of angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)