石菖蒲对抑郁大鼠脑内神经递质含量及行为学的影响

［摘要］　目的　探讨石菖蒲对抑郁大鼠脑内神经递质含量及行为学的影响。方法　将30只SD大鼠随机分为空白组、模型组、氟西汀组［1.8 mg/(kg·d)］、石菖蒲低剂量组［5 ml/(kg·d)］、石菖蒲中剂量组［10 ml/(kg·d)］和石菖蒲高剂量组［20 ml/(kg·d)］,每组5只。除空白组外,其余5组予以慢性、不可预见的温和刺激（CUMS）建造抑郁大鼠模型。通过强迫游泳试验(FST)、旷场试验(OFT)、高架十字迷宫试验(EPM)比较各组抑郁症状情况。比较各组大鼠脑组织多巴胺（DA）和5-羟色胺（5-HT）水平。结果　行为学实验结果显示,模型组游泳不动时间高于空白组,OFT得分、开放臂停留时间（OT）/两臂停留总时间（TT）低于空白组,差异有统计学意义（P<0.05）。模型组脑组织DA、5-HT水平显著低于空白组（P<0.05）。石菖蒲高剂量组、石菖蒲中剂量组、石菖蒲低剂量组、氟西汀组OFT得分、游泳不动时间、OT/TT较模型组改善,差异有统计学意义（P<0.05）。随着石菖蒲剂量的升高,大鼠脑组织DA、5-HT水平均呈上升趋势。石菖蒲高剂量组和氟西汀组脑组织DA、5-HT水平均显著高于模型组（P<0.05）,而与空白组比较差异无统计学意义（P>0.05）。结论　石菖蒲通过提高脑组织中的神经递质水平发挥抗抑郁作用。     

Effects of nephrectomy on hypertension, renin activity and total renal function in patients with chronic renal artery occlusion

Eight hypertensive patients (5 men and 3 women, aged between 31 and 64 years) with chronic total occlusion of one renal artery were observed for the past ten years. The peripheral plasma renin activity (PRA) and the renal vein PRA ratio (mean 3.18) were abnormally high in all cases. Because of the small size of the affected kidney (less than 9 cm in length), nephrectomy was the chosen treatment. Postoperative investigations revealed decreases in blood pressure (from 202/118 to 147/93 mmHg), peripheral PRA (from 6.05 to 1.05 ng/ml/h; P less than 0.001), serum creatinine (from 188.8 to 145.1 mumol/100 ml) urine volume (from 1937.5 to 1214.3 ml) and increases in endogenous creatinine clearance (from 36.57 to 53.0 ml/min). The results suggest that, apart from the decrease in blood pressure, the nephrectomy led to the disappearance of a factor which depresses the renal function in cases of chronic renal artery occlusion and which may be related to the renin-angiotensin system.     

Antihypertensive effects of captopril and saralasin in essential and renal hypertension

The antihypertensive effect of captopril and its mechanism of action were studied in patients with essential and renal hypertension. In mild essential hypertension (n = 12), during monotherapy with captopril (50 to 450 mg, 4 to 12 weeks) blood pressure was normalized in seven, improved in two and remained unchanged in three patients, plasma levels of active and acid-activatable inactive renin significantly increased and angiotensin II decreased, whereas no consistent changes in urinary kallikrein excretion occurred. In severe renal (n = 14) and essential (n = 9) hypertension, blood pressure was normalized in eight (seven with renal hypertension), improved in seven and unchanged in eight patients, when captopril (50 to 450 mg, 3 to 15 months) was added to the antihypertensive medication. In one patient with stenosis in a transplanted renal artery reversible renal failure occurred during captopril therapy possibly because of a steep initial decrease in blood pressure, although a toxic effect of the drug cannot be excluded. In another series of 12 renal and 8 essential hypertensive patients, a significant correlation between the acute effect of captopril (within 90 minutes) and saralasin on blood pressure was demonstrated (r = 0.71, p < 0.001). The change in blood pressure after either drug was significantly related to the initial plasma renin concentration.In conclusion, captopril sems to be an effective antihypertensive agent in essential and renal hypertension. Renal function should be monitored during captopril therapy. Our studies suggest that captopril decreases blood pressure by inhibiting the vasopressor action of the renin-angiotensin system.     

Effect of antihypertensive therapy on renal artery structure in type 2 diabetic rats with hypertension

We have previously demonstrated that antihypertensive treatment with doxazosin (DZN), an alpha-adrenergic blocker, and lisinopril (LIS), an ACE inhibitor, reverse glomerular sclerosis in corpulent spontaneously hypertensive rats with type 2 diabetes. In this study, we examined the effects of the above-mentioned antihypertensive drugs alone and in combination on the structure of interlobular and arcuate arteries in these rats. Both male and female rats aged 6 months were treated with antihypertensive drugs for 16 weeks. Various structural parameters were evaluated by light microscopy, with the use of digital image analysis, in kidney sections stained with periodic acid-SCHIFF: Systolic blood pressure was significantly lower in treated than in untreated rats. Untreated diabetic rats had a significantly higher media/lumen ratio (smaller luminal diameter) of both arteries compared with the ratio in treated rats (for interlobular artery, 0.72+/-0.06 [no treatment], 0.49+/-0.03 [DZN treatment], 0.54+/-0.06 [LIS treatment], and 0.52+/-0.04 [combination therapy], P<0.05 to <0.001 for no treatment versus treatment; for arcuate artery, 0.66+/-0.11 [no treatment], 0.40+/-0.02 [DZN treatment], 0.39+/-0.04 [LIS treatment], and 0.40+/-0.03 [combination therapy], P<0.05 for no treatment versus treatment). Antihypertensive treatment caused significant increases in total arterial cross-sectional area, internal and external diameters, luminal and medial cross-sectional area, and medial thickness in both interlobular and arcuate arteries. The improvement in arterial structure after antihypertensive treatment was due to remodeling and growth of the vessels. Both DZN and LIS were equally efficacious, and combination therapy had no additive or synergistic effect.     

大豆低聚肽对自发性高血压大鼠降血压作用的研究

目的探讨不同剂量的大豆低聚肽(SBOP)对自发性高血压大鼠(SHR)的降血压作用及其机制.方法6～8周龄雌性SHR大鼠30只及同周龄同体重Sprague-Dawley(SD)雌性大鼠6只随机分为A组(SHR对照组,饮水中不加SBOP及药物卡托普利)、B组[SBOP低剂量组,饮水中按100 mg/(L·d)加入SBOP]、C组[SBOP中剂量组,饮水中按500 mg/(L·d)加入SBOP]、D组[SBOP高剂量组,饮水中按1000 mg/(L·d)加入SBOP]、E组[卡托普利药物处理组,饮水中按50 mg/(L·d)加入卡托普利],F组[SD正常血压对照组,饮水中按1000 mg/(L·d)加入SBOP],实验期共30 d.尾袖法测定大鼠尾动脉血压,比色法测定血清及组织血管紧张素转换酶(angiotensin converting enzyme,ACE)活性.结果给予低、中、高3种剂量的SBOP 30 d后SHR大鼠血压分别为(155.5±15.6),(153.0±4.5),(151.5±5.0)mmHg,卡托普利药物处理组为(148.0±15.6)mmHg,SHR对照组为(174.0±11.5)mmHg,正常SD大鼠为(136.5±9.6)mmHg(P＜0.05).SBOP组与SHR对照组血清及主动脉ACE活性分别为(0.0118±0.069),(0.0121±0.0011),(0.0305±0.0048),(0.0290±0.0037)U(P＞0.05),而卡托普利药物处理组为(0.0054±0.0016),(0.0219±0.0039)U(P＜0.05).血清钠离子浓度SBOP、卡托普利药物处理组分别为(0.0896±0.0050),(0.0900±0.0012)μmol/L,SHR对照组为(0.1028±0.0056)μmol/L(P＜0.05).结论中、高剂量SBOP能有效地降低SHR大鼠的血压,且随剂量的增加血压有呈指数下降的趋势,但SBOP的降压效果始终不及降压药物卡托普利.SBOP对正常血压大鼠的血压无影响.SBOP降血压作用可能与降低外周组织液钠离子浓度有关,而与降低ACE活性无关.     

非洛地平对野百合碱所致大鼠肺动脉高压的作用

目的　利用野百合碱 (MCT)制作的大鼠肺动脉高压模型 ,探讨非洛地平对MCT所致肺动脉高压的作用。方法　雄性Wistar大鼠 30只 ,随机分为肺动脉高压模型组 (H组 ) ,非洛地平治疗肺动脉高压组 (F组 ) ,对照组 (C组 ) ,每组 1 0只。予MCT(60mg/kg)复制肺动脉高压大鼠模型后 ,分别给F组及C组大鼠非洛地平 (5mg·kg- 1 ·d- 1 )和生理盐水 (0 .5ml·kg- 1 ·d- 1 )腹腔注射 4周 ,然后测定右室收缩压 (RVSP)和静脉血浆及心、肺组织匀浆内皮素样免疫反应物 (ir ET)、降钙素基因相关肽(CGRP)的含量 ,观察电镜下心肌组织的改变。结果　H、F、C组大鼠RVSP分别为 (44.6± 4 .4)mmHg、(30 .3± 2 .1 )mmHg、(1 8.7± 2 .2 )mmHg ,三组间比较 (P分别 <0 .0 5、<0 .0 1 ) ;H、F组大鼠心、肺组织匀浆中CGRP分别为 (84± 1 9)pg/ml、(2 2± 4)pg/ml、(2 0 .9± 1 .6)pg/ml,(1 4 9± 2 1 )pg/ml、(2 9± 3)pg/ml、(2 7.5± 2 .9)pg/ml,两组间比较 (P <0 .0 5)。非洛地平能显著抑制MCT大鼠模型引起的肺小动脉中膜肥厚 ,减少心肌组织的破坏 ,抑制MCT所致肺动脉高压大鼠模型的血浆及CGRP的减少。结论　长期使用非洛地平能有效防治MCT所致肺动脉高压 ,其作用可能与其Ca2 + 拮抗作用及CGRP降解减少有关。     

Antihypertensive effect of cicletanine is exaggerated in NaCl-sensitive hypertension.

Cicletanine (CIC), a furopyridine derivative, lowers blood pressure in hypertensive animals and humans. We have previously identified an NaCl-sensitive substrain of spontaneously hypertensive rat (SHR-S) that displays enhanced sensitivity to the depressor effects of exogenous atrial natriuretic peptide (ANP) when fed a high NaCl diet. The current study tested the hypotheses that CIC has an exaggerated antihypertensive effect in NaCl-supplemented SHR-S and that this effect might be ANP dependent. CIC (40 mg/kg/day) or vehicle was administered by gavage in a single daily dose for three weeks beginning immediately prior to initiation of 1% or 8% NaCl diets in seven-week-old male SHR-S. CIC significantly decreased mean arterial pressure (MAP) and the ratio of left ventricular and septum weight to body weight (LV + S/BW) in both 8% NaCl- and 1% NaCl-fed SHR-S. The depressor effect of CIC was greater in the 8% NaCl group (-26 mmHg) than in the 1% NaCl group (-13 mmHg). CIC was associated with significant reduction in RAP in the 8% NaCl group but not in the 1% NaCl group. Neither CIC treatment nor 8% NaCl significantly altered plasma ANP or cyclic guanosine monophosphate (GMP) levels in plasma, aorta, or kidney. CIC was associated with significant decreases in plasma norepinephrine (NE) levels in the 1% NaCl group but not in the 8% NaCl group. The data demonstrate that the antihypertensive effect of CIC is exaggerated in NaCl-sensitive hypertension. The antihypertensive effect of CIC appears not to be related to ANP or cyclic GMP but may be related to a combination of a sympatholytic and natriuretic/diuretic effects in SHR-S.     

Renal vein renin measurements accurately identify renovascular hypertension caused by total occlusion of the renal artery

OBJECTIVE : To assess the usefulness of indexes derived from renal vein renin measurements. DESIGN : A 12-year prospective study. SETTING : A tertiary institutional referral centre. PATIENTS AND METHODS : Between 1988 and 2000, we studied 152 consecutive hypertensive patients with a high pre-test probability of renovascular hypertension (RVH). RVH was diagnosed retrospectively on the basis of reduction in blood pressure after correction of ischaemia at follow-up. Renal vein renin measurements were used to calculate the ratios: Visch/Vctl (renal vein renin ratio; RVRR); Vctl/Viivc; (Visch - Viivc)/Viivc; (Vctl - Viivc)/Viivc, where Visch and Vctl indicate plasma renin activity (PRA) in the ischaemic and contralateral renal veins, respectively, and Viivc denotes PRA in the infrarenal inferior vena cava. A receiver operator characteristics (ROC) curve analysis was used to determine the cut-off value of renal vein renin measurement indexes that provided the best discrimination between patients with and without RVH and to identify patients with RVH caused by total occlusion of the renal artery. RESULTS : Sixty-seven patients were diagnosed as having RVH: 51 had significant renal artery stenoses (RVH non-occluded) and 16 had total renal artery occlusion (RVH occluded). Of the remaining 85 patients in whom RVH was excluded (non-RVH group), 27 had reno-parenchymal hypertension and 58 had essential hypertension. Of the renal vein renin measurement indexes, only RVRR and (Visch - Viivc)/Viivc in RVH-occluded patients differed significantly (P < 0.005) from those in the non-RVH group and showed the best performance by ROC curve analysis. This analysis also showed that, at any cut-off value, RVRR was far more accurate for identification of RVH-occluded patients than for identification of RVH non-occluded patients, both in the subgroup with unilateral and, even more so, in those with bilateral renal artery lesions. The best trade-off between sensitivity and false-positive rate was provided by cut-off values of 1.55 and 1.70 of the RVRR for identification of non-occluded and occluded RVH, respectively. CONCLUSIONS : RVRR is more useful for establishing an indication for nephrectomy in patients with renal artery occlusion than for identifying those patients with renal artery stenosis who will benefit from revascularization. In patients with RVH with bilateral renal artery lesions, lateralization of renin secretion occurs only in the presence of total renal artery occlusion. Different cut-off values are necessary for identification of non-occluded and occluded RVH.     

多西环素预防肾性高血压大鼠脑动脉瘤形成的机制研究

目的观察多西环素对肾性高血压大鼠脑动脉瘤形成的抑制作用及其对基质金属蛋白酶(matrixmetalloprotei-nase,MMPs)活性的影响。方法雄性SD大鼠90只,制作大鼠脑动脉瘤模型,随机分为对照组(10只)、模型组(40只)和治疗组(40只),光镜及电镜观察组织学变化,应用免疫组织化学及逆转录聚合酶链反应检测基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)的动态变化。结果对照组没有动脉瘤产生,其脑动脉壁MMP-2、MMP-9活性微弱;模型组动脉瘤发生率20%,随着大鼠血压的增加,其脑动脉壁MMP-2、MMP-9活性迅速增加,在术后1个月基本达最高峰并一直持续至4个月。治疗组仅发现部分动脉呈瘤前病变,无明显的动脉瘤产生,其动脉壁MMP-2、MMP-9活性被明显抑制,随着大鼠血压的增加,MMP-2、MMP-9活性仅有轻度增加,无明显的活性高峰出现。结论多西环素可能通过抑制脑动脉瘤形成过程中异常增高的MMP-2、MMP-9活性,从而阻止脑动脉瘤的发生。     

Antihypertensive effect of enalapril in essential hypertension: role of prostacyclin

The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive effect of thymectomy in Lyon hypertensive rats Vascular reactivity,renal histology,and sodium excretion

The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.     

Antihypertensive effect of sweetie fruit in patients with stage I hypertension

BACKGROUND: Interventional studies have shown that increased intake of fruit and vegetables reduces blood pressure (BP). However, the contribution of specific dietary components has not been evaluated. The aim of the present study was to determine, in patients with stage I hypertension, the antihypertensive effect of juice of the so-called sweetie fruit (a hybrid between grapefruit and pummelo) with and without high flavonoid content. METHODS: A double-blind, cross-over study was conducted in 12 patients. Each patient received alternately high-flavonoid (HF) sweetie juice and low-flavonoid (LF) sweetie juice, each for a 5-week period. The LF sweetie juice had 25% of naringin and 30% of narirutin content compared with the original HF sweetie juice. RESULTS: The HF sweetie juice was more effective than LF sweetie juice in reducing diastolic blood pressure (P = .04). Systolic blood pressure declined in both groups; however there was no significant difference between subjects given HF sweetie versus those given LF sweetie juice. CONCLUSIONS: In this study HF sweetie juice was shown to have a significant beneficial effect in reducing diastolic blood pressure, compared with the effect observed with LF sweetie juice, in patients with stage I hypertension. These data suggest that the active ingredients associated with the antihypertensive effect of sweetie juice are the flavonoids naringin and narirutin.