短期输注L-精氨酸对血压的影响

通过１５例原发性高血压病人及１４例正常对照者静脉输注Ｌ－精氨酸前后血浆Ｌ－精氨酸浓度及血压变化的观察，发现补充Ｌ－精氨酸能迅速提高原发性高血压人及正常对照组血浆Ｌ－精氨酸浓度，同时降低两组受试者平均动脉压，结果提示补充外源性Ｌ－精氨酸对原发性高血压及健康人血压的影响是相似的。     

L—精氨酸及其N衍生物对高血压大鼠离体血管的舒张作用

用Ｌ－精氨酸及Ｌ－精氨酸Ｎ端ａ衍生物Ｎ－乙酰精氨酸、Ｎ－苯甲酰精氨酸，对原发性高血压大鼠离体主动脉血管平滑肌的舒张作用进行研究，并与正常血压大鼠的主动脉血管平滑肌做比较。     

精氨酸及其衍生物体外血管活性作用评价（摘要）

精氨酸及其衍生物体外血管活性作用评价（摘要）中国人民解放军空军总医院药剂科王峰，吉小莉用Ｌ－精氨酸（Ｌ－Ａｒｇ）及Ｌ－精氨酸Ｎ衍生物Ｎ－乙酰精氨酸（Ｎ－Ａｃ－Ａｒｇ）、苯甲酰Ｌ－精氨酸（Ｂｅ－Ａｒｇ）对正常血压大鼠及原发性高血压大鼠离体动脉血管的舒张...     

细胞内胞浆游离钙、血管紧张素Ⅱ和动态血压改变与氨氯地平血药浓度变化的关系

目的观察氨氯地平的降压作用与其血浆血药浓度、细胞内胞浆游离钙浓度（[Ca2＋]i）、血管紧张素Ⅱ浓度（[AT－Ⅱ]）和24h动态血压改变的关系。方法给14名原发性高血压病人及性别、年龄严格匹配的正常对照组口服单剂量（5mg）氨氯地平治疗，治疗前后检测上述指标。结果原发性高血压病人之[Ca2＋]i和[AT－Ⅱ]比正常对照组显著升高。口服单剂量氨氯地平治疗后，随着血药浓度上升，血压、[Ca2＋]i和[AT－Ⅱ]显著下降。药物作用的高峰在服药后的6h，且其药物作用可维持24h。治疗后[Ca2＋]i的下降幅度、血药浓度的上升幅度、血压的下降幅度和[AT－Ⅱ]的下降幅度之间有明显的相关性。原发性高血压病人经氨氯地平治疗后，24h平均血压显著下降，降压谷：峰值比率：收缩压力79．27％，舒张压为68．40％。结论以上资料提示：氨氯地平能平稳、有效地降低高血压病人的血压而且其药物作用能维持24h，其降压作用可能通过降低细胞内胞浆游离钙浓度和血管紧张素Ⅱ的浓度而发挥作用。     

静滴L—精氨酸对原发性高血压影响的研究

从血流动力学及神经内分泌学两方面探讨左旋精氨酸（Ｌ－Ａｒｇ）－一氧化氮（ｎｉｔｒｉｃｏｘｉｄｅ，ＮＯ）通路对原发性高血压的影响。方法２６例高血压病人分为两组，一组静滴Ｌ－Ａｒｇ，一组静滴生理盐水，观察其血压、心率及心功能的变化，同时检测血中ＮＯ、ｃＧＭＰ、肾上腺素（Ｅ）、去甲肾上腺素（ＮＥ）以探讨其降压机理。结果在Ｌ－Ａｒｇ静注期间，病人血压下降，心率增快，心输出量（ＣＯ）、每搏输出量（ＳＶ）、射血分数（ＥＦ）增加，总外周阻力（ＴＰＲ）降低，ＮＯ的标志物ｃＧＭＰ升高。而在滴注６０＇时，随着ｃＧＭＰ浓度的降低，ＣＯ、ＳＶ、ＥＦ也随之降低，而ＴＰＲ复又回升。Ｅ、ＮＥ、Ｎｉｔｒｉｔｅ及Ｎｉｔｒａｔｅ在静滴前后无显著性改变。结论Ｌ－Ａｒｇ通过使ｃＧＭＰ浓度升高，引起明显的血流动力学改变；Ｌ－Ａｒｇ可能抑制血压过低所致的反应性Ｅ及ＮＥ的升高作用。     

高血压患者血浆精氨酸加压素变化

目的测定高血压患者血浆精氨酸加压素变化。方法，应用放射免疫法测定１２０例高血压患者及６０例正常人的血浆免疫活性精氨酸加压素（ｉｒ－ＡＶＰ）含量。结果，发现同血压组血浆ｉｒ－ＡＶＰ水平明显高于正常对照组（Ｐ〈０．０１）。病程≥１０年者的ｉｒ－ＡＶＰ高于〈１０年者（Ｐ〈０．０１）。Ⅲ期设备是的血浆ｉｒ－ＡＶＰ焦点量明显主于Ⅰ、Ⅱ期者（Ｐ〈０．０１），患者组血浆ｉｒ－ＡＶＰ与血压水平，血浆肾素活性及血管     

口服L-精氨酸对腹主动脉缩窄后大鼠血压、心肌肥厚和血管舒张功能的影响

本文利用缩窄大鼠腹主动脉的方法制备高血压模型，观察了正常大鼠、未服和口服Ｌ－精氨酸两周的腹主动脉狭窄的大鼠的血压、心肌肥厚及血管舒张功能的改变，旨在了解Ｌ－精氨酸对腹主动脉缩窄性高血压大鼠的作用。研究发现腹主动脉狭窄后大鼠发生了严重的高血压及心肌肥厚。未服Ｌ－精氨酸的大鼠心肌肥厚，且血管环对１０－８～１０－５ｍｏｌ／Ｌ乙酰胆碱诱导的舒张反应明显减低；而Ｌ－精氨酸口服治疗两周能减轻其心肌肥厚，并部分改善乙酰胆碱诱导的血管舒张功能，但两组大鼠腹主动脉缩窄后的血压均升高，两者相比较差别无统计学意义（Ｐ＞０．０５）。结果提示：Ｌ－精氨酸（１０－５～１０－３ｍｏｌ／Ｌ）有直接舒张该大鼠血管环的作用，且呈剂量依赖关系，长期口服Ｌ－精氨酸可减轻腹主动脉缩窄性大鼠的心肌肥厚，改善其血管的舒张功能，而其血压的变化与上述作用无关。     

血浆内源性阿片肘升高与肝硬化外周动脉扩张及腹水形成的关系

目的：探讨血浆三种内源笥阿片肽浓度变化，以了解它与肝硬化外周动脉扩张及腹水形成的关系。方法：用辨免法检测了２０例正常人，２０例非肝病及５０例肝硬化患者的血浆强啡肽（ＤｙｎＡ１－１３），亮啡肽（Ｌ－ＥＮＫ）和β－内啡肽（β－ＥＰ）。结果：肝硬化无腹水组和有腹水组血浆ＤｙｎＡ１－１３和Ｌ－ＥＮＫ浓度均明显高于正常对照组和非肝病对照组（Ｐ〈０．０１）；随病情加重，ＤｙｎＡ１－１３和Ｌ－ＥＮＫ均呈上升趋势     

高血压病人纤维蛋白原水平及纤溶系统功能研究

为了解高血压病人的血栓形成倾向,我们随机选取了４１例高血压病人及３４例正常血压者,分别观察了他们的纤维蛋白原及血浆组织型纤溶酶原激活物（ｔＰＡ）抗原及纤溶酶原激活物抑制物－１（ＰＡＩ－１）的含量。结果表明,高血压病人血浆纤维蛋白原水平无明显变化,但ｔＰＡ抗原含量减少,ＰＡＩ－１的水平增加。提示高血压病人存在内源性纤溶功能受损     

高血压病合并高胰岛素血症患者血浆凝血■烷B_2及6－酮－前列腺素F_（1α）的变化

目的：研究血浆凝血烷Ｂ２（ＴＸＢ２，血栓素Ｂ２）及６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）在原发性高血压（高血压病）伴高胰岛素血症患者中的变化。方法：对４０例高血压病伴高胰岛素血症患者及３０例正常人进行口服糖耐量、胰岛素释放水平测定，在糖耐量过程中进行血压、血浆ＴＸＢ２及６－ｋｅｔｏ－ＰＧＦ１α的观察。结果：与正常组比较，高血压病组基础及糖刺激后血浆胰岛素水平显著升高（Ｐ＜０．０５），ＴＸＢ２增高（Ｐ＜０．０１）及６－ｋｅｔｏ－ＰＧＦ１α水平显著下降（Ｐ＜０．０５）。结论：高血压合并高胰岛素血症时，血浆ＴＸＢ２增高、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值升高在高血压的发生发展中起着重要作用。     

Effects of oral L-arginine on plasma nitrate and blood pressure in cortisol-treated humans

OBJECTIVE: The aim of this study was to determine whether cortisol-induced hypertension can be reversed by co-administration of oral L-arginine. STUDY DESIGN: Three studies were undertaken in healthy male human subjects. The first study addressed the effect of oral L-arginine loading on plasma arginine concentration. Study 2 addressed the effect of co-administration of cortisol with L-arginine on plasma L-arginine concentrations. Study 3 was a randomized placebo crossover control comparing the effects of cortisol 80 mg/day co-administered with a placebo to cortisol 80 mg/day co-administered with L-arginine 21 g/day. METHODS: Blood pressure was measured by a random Hawksley sphygmomanometer. Plasma nitrate/nitrite concentrations were measured by a modified Greiss reaction. Plasma arginine and citrulline concentrations were measured by an automated amino acid analyser. RESULTS: Plasma arginine concentrations were doubled by oral doses of 15 g/day and 21 g/day of L-arginine (study 1). Co-administration of cortisol did not alter plasma arginine concentrations in subjects taking 21 g of L-arginine per day (study 2). Co-administration of L-arginine 21 g/day with cortisol 80 mg/day did not prevent cortisol-induced increases in blood pressure or cortisol-induced falls in plasma nitrate/nitrite concentrations. CONCLUSION: Cortisol-induced hypertension is accompanied by a fall in plasma nitrate/nitrite concentrations. Oral L-arginine administration does not prevent cortisol-induced falls in plasma nitrate/nitrite concentrations or increases in blood pressure. We propose that cortisol-induced reductions in nitrate/nitrite production occur at a point distal to L-arginine availability in the nitric oxide synthase pathway.     

L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat

BACKGROUND: L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L-arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L-arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D-arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH-induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats.     

The Central Effects of a Nitric Oxide Synthase Inhibitor (Nω - Nitro - L - Arginine) on Blood Pressure and Plasma Renin

An endothelium-derived relaxing factor has been identified as nitric oxide (NO). Peripheral and central administration of nitric oxide synthase inhibitors result in an increase in renal sympathetic nerve activity and an increase in blood pressure. The goal of our study was to determine if the increase in blood pressure following central NO synthase inhibition with NM-nitro-L-arginine (L-NNA) is caused by the release of renin. Six groups of Sprague-Dawley rats were used. Group I (control) received intracerebroventricular (i.c.v.) artificial cerebrospinal fluid. Groups II & III received i.c.v. L-NNA, 5 & 15 μg/min. respectively. Group IV was treated with intravenous L-NNA, 15 μg/min. Group V, after bilateral nephrectomy, received i.c.v. L-NNA, 15 μg/min. Group VI received i.c.v. L-arginine, 60 μg/min. and i.c.v. L-NNA, 15 μg/min., simultaneously. Plasma renin concentration was measured in groups I, III, IV & V. Mean arterial blood pressure was significantly increased in groups II, III & V, i.e., following i.c.v. infusion of L-NNA. The increase in mean arterial blood pressure was significantly greater when the dose was increased from 5 to 15 μg/min. and it was eliminated when L-arginine was added to the infusion. The increase in blood pressure was attended by no change in heart rate. While the plasma renin concentration increased significantly in group III, this could not explain the increase in blood pressure since the nephrectomized group (V) showed no increase in renin concentration but an equivalent increase in blood pressure. The results show that acute central administration of a low dose of L-NNA increases blood pressure in rats and this increase can be prevented by central.     

The effect of oral administration of L-arginine on anal resting pressure and anodermal blood flow in healthy volunteers

BACKGROUND: Topical application of L-arginine, the precursor of nitric oxide, reduces anal resting pressure without significant side effects and may therefore be of benefit in the treatment of anal fissure. This in vivo study investigated the effect of orally administered L-arginine on anal resting pressure and anodermal blood flow in healthy volunteers. METHODS: Eight healthy volunteers took 3 sachets of Arginaid (Novartis Consumer Health, Breda, The Netherlands) containing 15 g L-arginine on a daily basis, for 7 days. At the start of the experiment (day 0) and on days 3 and 7, plasma levels of L-arginine, anal resting pressures and anodermal blood flow were determined. RESULTS: Arginine plasma levels increased from 107.0+/-8.6 micromol/l (day 0) to 283.7+/-44.0 micromol/l on day 3 (p< 0.01) and remained elevated at day 7 (157.3+/-19.6 micromol/l, p<0.05). Anodermal blood flow and anal resting pressures were similar on days 0, 3 and 7. CONCLUSIONS: Oral administration of 15 g arginine in healthy volunteers on a daily basis increased arginine plasma levels but had no influence on anodermal blood flow and anal resting pressure.     

Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man.

The effects of L-arginine administration on systemic hemodynamics and plasma concentrations of neuro-endocrine hormones and amino acids were investigated in 10 normotensive healthy volunteers. Nitrite/nitrate in urine and cyclic guanosine monophosphate (c-GMP) in plasma were also measured as indicators of release of nitric oxide (NO). L-arginine administration (30 g/300 ml/30 min) caused hypotension (mean arterial pressure; 79.3 +/- 3.9 mmHg fell to 68.8 +/- 2.2 mmHg) with tachycardia (62.3 +/- 2.3 beats/min increased to 67.5 +/- 1.9 beats/min). The plasma concentration of L-arginine before administration was 98.8 +/- 8.2 mumol/l and increased to 7263 +/- 567 mumol/l 20 min after administration. Cardiac output also increased to 127.2 +/- 3.9% by L-arginine administration. Total peripheral resistance was calculated to fall to 65.9 +/- 2.0%. L-arginine administration slightly changed several hormones, but all values were within normal ranges. Nitrite/nitrate in urine increased 142.1 +/- 12.4% compared to the values before L-arginine administration. Plasma concentrations of c-GMP and L-citrulline, the by-product of NO from L-arginine, were also significantly increased by L-arginine administration. All our results provide evidence for the first time that systemically administered L-arginine releases NO in man.     

Low-dose L-arginine administration increases microperfusion of hindlimb muscle without affecting blood pressure in rats

The objective of this work was to evaluate the influence of exogenous L-arginine on the capillary blood flow of peripheral tissues of normotensive subjects. Rats were anesthetized with sodium pentobarbital, and the blood flow of femoral, dorsal, and ventral skin and gastrocnemius and soleus muscle was measured by laser Doppler flow and microsphere methods to compare the blood flow before and after the L-arginine infusion. L-arginine lowered the mean blood pressure in a dose-dependent manner, but a statistically significant reduction in mean blood pressure was detected only at a high dose of 500 mg/kg of body weight. The significant blood flow increment was detected after the L-arginine infusion at doses of 50 and 150 mg/kg without causing hypotension. Nicardipine, a calcium channel blocker, also increased the skin blood flow, but the blood flow increment and blood pressure fall were comparable. A significant increment in microperfusion was detected in gastrocnemius, soleus muscle, and ventral skin compared with control group by the microsphere method. No adverse effects were observed during L-arginine and microsphere infusion. The present work indicates that l-arginine infusion increases muscle capillary blood flow in rats that are not performing exercise. Supplementation with l-arginine might provide additional blood flow at rest and during exercise and result in the improvement of muscle performance and exercise capacity.     

Control of regional blood flow by endothelium-derived nitric oxide

The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation with NG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3-300 mg/kg) caused a dose-dependent, long-lasting (5-90 minutes), and enantiomerically specific increase in mean blood pressure and also caused bradycardia. The increase in blood pressure was accompanied by a dose-dependent and long-lasting vasoconstriction in the internal carotid, mesenteric, renal, and hindquarters vascular beds that could be attenuated, in a concentration-dependent manner, by L-arginine but not by D-arginine. In contrast, L-arginine did not affect the pressor or vasoconstrictor effects of vasopressin. These results indicate that nitric oxide production by vascular endothelial cells contributes to the maintenance of blood pressure and to the control of the resting tone of different vascular beds in the conscious rat.     

Blood pressure profile and variability in hypertensives treated with L-arginine infusion

BACKGROUND: The role of nitric oxide (NO) in regulation of systemic blood pressure both in normotensives and in hypertensives remains unknown. OBJECTIVE: To investigate the influence of L-arginine (the substrate for generation of NO) on blood pressure in 30 men (aged 51.5 +/- 7.3 years) with established primary arterial hypertension that was not well controlled. METHODS: The antihypertensive therapy was not discontinued and the patients were administered beta-blockers and calcium antagonists only. On day '0' the patients were administered 250 ml 0.9% NaCl during 180 min intravenously. Then we infused 250 mg/kg L-arginine diluted in 250 ml 0.9% NaCl over 180 min into the antecubital vein for four consecutive days (days 'I'-'IV'). Conventional blood pressure and heart rate measurementws were performed before infusion and every 30 min during infusion. Twenty-four-hour ambulatory blood pressure monitoring (with a SpaceLabs 90207 device) with half-hourly recordings during the daytime and during the night-time was performed on the day of NaCl infusion ('0') and repeated on the day of L-arginine infusion ('II') for all patients. As indicators of generation of NO, blood level of cyclic GMP and urinary concentration of nitrite/nitrate were measured. RESULTS: On all days of L-arginine infusion we found significant falls in systolic and diastolic blood pressures (P < 0.0001) with an accompanying significant increase in heart rate (P < 0.001). The most potent hypertensive effect during infusion of L-arginine was observed on day 'I'. Mean systolic blood pressure decreawsed from 152.1 +/- 20.0 mmHg to a minimum of 123.3 +/- 16.2 mmHg after 60 min of the infusion (by about 19%). The maximal percentage fall in systolic blood pressure was consecutively lower on each day oif L-arginine infusion. It was 14.3% on day 'II', 11.9% on day 'III' and 10.1% on day 'IV'. Similarly, the greatest reduction of diastolic blood pressure was observed during infusion of L-arginine on day 'I'. Mean diastolic blood pressure decreased from 95.9 +/- 13.6 to 80 +/- 9.7 mmHg after 120 min of infusion (by about 17%). On the consecutive days maximal falls in diastolic blood pressure compared with its initial value were 13.5% on day 'II', 10.4% on day 'III' and 9.8% on day 'IV'. Twenty-four-hour ambulatory blood pressure monitoring revealed a significant decrease in diastolic blood pressure during infusion of L-arginine compared with day 0 when 0.9% NaCl was infused. Systolic and diastolic blood pressure variabilities were significantly decreased and the day-night differences in systolic and diastolic blood pressures were increased after infusion of L-arginine. We found a significant correlation between heart rate and systolic blood pressure both during the daytime and during night-time on the day of infusion of L-arginine. An increase in urinary concentration of nitrite/nitrate was observed after administration of L-arginine.CONCLUSION: The present results demonstrate that infusion of L-arginine can influence the systemic blood pressure in hypertensives through NO synthesis. By using ambulatory blood pressure monitoring we documented that the hypotensive effect of L-arginine seems to be limited to the infusion period itself. A decrease in blood pressure variability might imply an increase in sensitivity of baroreceptors or an improvement of autonomic functioning.     

Sexual dimorphism in vasopressin and cardiovascular response to hemorrhage in the rat

There is evidence for sex-related differences in the cardiovascular actions of vasopressin. Furthermore, receptors for the gonadal steroid hormones are located in centers in the brain involved in the control of vasopressin release and in cardiovascular regulation. We have, therefore, examined the effects of hemorrhage on mean arterial blood pressure, the plasma vasopressin concentration, and plasma renin concentration in conscious male and female rats. In preliminary experiments, no differences were found in blood and plasma volumes with respect to either sex or phase of the estrous cycle. In separate experiments, rats were subjected to two hemorrhages of 10% of blood volume, separated by an interval of 15 minutes. There were no substantial gender- or cycle-related differences in the ability of hemorrhaged rats to maintain mean arterial blood pressure or increase plasma renin concentration. The increase in plasma vasopressin concentration was greater in proestrous females than in males after the first hemorrhage and in diestrous, proestrous, and metestrous females than in males after the second hemorrhage. Pretreatment with a V1-receptor antagonist was without statistically significant effect on the mean arterial blood pressure responses in males, but it impaired blood pressure compensation in females. There are, then, gender- and cycle-related differences in vasopressin responses to hemorrhage, and vasopressin appears particularly important for blood pressure compensation to hemorrhage in female rats.