PROTECTIVE EFFECT OF TREATMENT WITH NICARDIPINE ON CEREBROVASCULAR TREE OF SPONTANEOUSLY HYPERTENSIVE RATS

The effect of an eight-week treatment with the Ca²⁺ channel blocker nicardipine on different-sized pial arteries and intracerebral arteries was assessed in spontaneously hypertensive rats (SHR) by microanatomical techniques. Normotensive Wistar-Kyoto (WKY) rats were used as normotensive reference animals. In SHR a significant increase of systolic blood pressure (SBP) in comparison with WKY rats was noticeable. An increased thickness of tunica media and luminal narrowing were also seen in medium- and small-sized pial arteries, and in intracerebral arteries of SHR in comparison with WKY rats. The media-to-lumen ratio was also increased in medium (diameter between 150 and 50 μm) and small-sized (diameter < than 50 μm) pial and intracerebral arteries. Treatment with nicardipine significantly reduced SBP, the thickness of tunica media, media-to-lumen ratio and increased luminal area of medium- and small-sized pial arteries and of intracerebral arteries. These findings demonstrate that treatment of SHR with nicardipine induces a moderate vasodilatation of both pial and intracerebral arteries regulating cerebrovascular resistance.

This property may be useful in avoiding generalized or exaggerated cerebrovascular dilatation in hypertension which could be accompanied by impaired brain perfusion.     

LACK OF INHIBITION OF ANTERIOR PITUITARY HORMONE RELEASE DURING CHRONIC TREATMENT WITH CALCIUM ANTAGONISTS

Calcium antagonists are widely used for the treatment of cardiovascular disorders, especially ischaemic heart disease. It has been demonstrated that these drugs, either in vitro or acutely administered in humans, inhibit the basal and stimulated secretion of pituitary hormones by blocking calcium influx through slow calcium channels. To see if a similar effect could be detected after their chronic administration, we studied the basal, TRH- and LHRH-stimulated TSH, PRL, LH and FSH release in 18 male subjects with chronic stable angina before and on the 30th day of oral treatment with verapamil (n=8; 80 mg three times a day) or with nifedipine (n=10; 10 mg three times a day). Neither drug had any effect on basal TSH, PRL, LH and FSH values or on their response to the specific hypothalamic-releasing hormones. These results suggest that the chronic administration of calcium antagonists, at the usual therapeutic doses, does not effect the process of stimulus-secretidn coupling of anterior pituitary hormones, ruling out any impairment of the related target glands which have been expected on the basis of previous studies.     

EFFECT OF NICARDIPINE TREATMENT ON THE EXPRESSION OF NEUROFILAMENT 200 KDa IMMUNOREACTIVITY IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS

Neurofilaments (NFP) are components of neuronal cytoskeleton involved primarily in axonal transport and in the regulation of dynamic activities of nerve cells. NFP consist of three subunits denominated high- (200 kDa, NFP–H), intermediate- (160 kDa, NFP-I), and low-molecular weight (68 kDa, NFP–L) neurofilament proteins. Their function and polymerization depends on phosphorylation status, and is regulated by Ca²⁺ influx. Ca²⁺ overload enhances degradation of NFP and may compromise axonal transport. An increased susceptibility to ischemia occurs in hypertension, which is also a cause of brain damage. In this study, the expression of phosphorylated NFP (P–NFP) was investigated in the brain of spontaneously hypertensive rats (SHR) using immunohistochemical techniques with antibodies against the phosphorylated epitope of NFP RT–97. Microanatomical analysis included frontal cortex, occipital cortex, hippocampus and cerebellar cortex. The effect of long-term treatment with the dihydropyridine-type Ca²⁺ antagonist nicardipine on the expression of P–NFP was investigated as well. In hypertension a decreased P–NFP immunoreactivity was observed in frontal and occipital cortex, in the CA1 subfield of hippocampus and in the dentate gyrus, but not in the CA3 subfield of hippocampus or in the cerebellar cortex. Treatment with a daily dose of 3 mg/kg of nicardipine and 10 mg/kg of hydralazine significantly reduced systolic pressure in SHR. The above dose of nicardipine and to a lesser extent a non-hypotensive dose of the compound (0.1 mg/kg/day), but not hydralazine, increased P–NFP immunoreactivity in the cerebral cortex and hippocampus, except the CA3 subfield. The possibility that rescued P–NFP immunoreactivity by treatment with nicardipine depends on improved brain perfusion caused by the compound and/or by countering neuronal Ca²⁺ overload is discussed.     

依那普利对NIDDM并微白蛋白尿患者的作用

在无明显临床肾病征象的177例NIDDM中检出微白蛋白尿患者18例(10.2％)。采用单盲随机交叉实验设计,对其中14例用血管紧张素转换酶(ACE)抑制剂依那普利(Enalapril,E)和钙通道阻滞剂尼群地平(Nitrendipine,N)治疗。结果表明E不但是NIDDM合并高血压患者的有效降压药之一,且对正常血压或高血压NIDDM合并微白蛋白尿者,具有不依赖于其降压效应而减少尿蛋白的作用     

钙拮抗剂对3T6成纤维细胞的影响

采用流式细胞技术（ＦＣＭ）观察不同剂量的四种钙拮抗剂（Ｃａ－Ａ）汉防已甲素（Ｔｅｔ）、硝苯啶（Ｎｉｆ）、维拉帕咪（Ｖｅｒ）及脑益嗪（Ｃｉｎ）对３Ｔ６成纤维细胞生长增殖的影响，结果表明它们不仅可阻断Ｇ１→Ｓ期的进程，而且抑制Ｓ期ＤＮＡ的含量，但却增加Ｇ１和Ｇ２期蛋白质的含量，使细胞呈现不平衡生长，最终死亡。其中Ｔｅｔ的作用最为显著，呈一定的量效关系，此作用与阻断钙离子内流无关。提示钙拮抗剂对３Ｔ６成纤维细胞生长增殖的抑制可能是其抗肝纤维化的机制之一。     

EFFECTS OF NG-NITRO-L-ARGININE ON THE BLOOD PRESSURE OF SPONTANEOUSLY HYPERTENSIVE RATS WITH DIFFERENT DEGREES OF HYPERTENSION

The effects of N^G-nitro-L-arginine (L-NNA) on blood pressure of various strains of spontaneously hypertensive rats were studied. Blood pressure of the rats was higher in the order of WKY, SHR, SHRSP, M-SHRSP. L-NNA caused an elevation of the blood pressure, which was greatest in SHR and smallest in WKY and M-SHRSP. Endothelium-dependent relaxation of aortae by acetylcholine was greatest in preparations from WKY and it decreased as the blood pressure of rats increased. Phenylephrine (higher than 10^?6mg/kg) caused an elevation of the blood pressure, which was greatest in SHR and smallest in M-SHRSP. It was suggested that L-NNA elevated blood pressure by inhibiting the basal or flow-induced release of nitric oxide from the endothelium that is causing a reduction in vascular smooth muscle tone. The smaller effect of L-NNA in WKY was due to weak smooth muscle tone, while the smaller effect in SHRSP and M-SHRSP is due to impaired function of endothelium.     

EFFECT OF ANTIHYPERTENSIVE TREATMENT ON PERIPHERAU NERVE VASC UATRE IN SPONTANEO SUY HYPERTENSIVE RATS

The influence of hypertension and of treatment with the dihydropyridine-type Ca⁺² antagonist nicardipine on peripheral nerve vasculature were investigated in spontaneously hypertensive rats (SHR). Male SHR were treated from the 16th to the 26th week of age with vehicle (control group), with nicardipine, at the hypotensive dose of 3 mg/kg/day, or at the nonhypotensive dose of 0.1 mg/kg/day or with an equihypotensive dose (10 mg/kg/day) of the nondihydropyridine-type vasodilator hydralazine. Age-matched normotensive Wistar-Kyoto (WKY) rats were left untreated and used as normotensive reference animals. In SHR a significant increase of systolic pressure values accompanied by sciatic nerve microvascular changes, involving primarily interfascicular arteries and to a lesser extent intrafascicular arteries, was observed. Treatment with the hypotensive dose of nicardipine countered hypertension-dependent microvascular changes occurring in both interfascicular and intrafascicular arteries. The nonhypotensive dose of nicardipine and hydralazine displayed a modest activity on interfascicular arteries, but significantly countered hypertension-related changes involving intrafascicular arteries.

The above findings indicate the occurrence of hypertension-related changes of peripheral nerve microvasculature and of positive effects induced by appropriate pharmacological treatment. Further work is in progress to identify the functional relevance of microanatomical observations of the present study.     

EFFECT OF CHRONIC TREATMENT WITH LOSARTAN ON STREPTOZOTOCIN INDUCED DIABETIC NEPHROPATHY

Angiotensin converting enzyme (ACE) inhibitors produce a number of beneficial effects in a condition where diabetes - mellitus and hypertension co-exist. The present investigation was undertaken to study the effect of chronic treatment with losartan (2mg/kg, p.o.) on streptozotocin(STZ)-induced (45mg/kg, single dose, tail vein) diabetic nephropathy in rats. Treatment of ratswith STZ produced a significant loss of body weight, polyuria, polydipsia, hypoinsulinemia, hyperglycemia and increase in blood pressure. There was a significant increase in blood glucose levels in STZ-diabetic rats. Serum cholesterol, creatinine, urea and blood urea nitrogen (BUN) levels were found to be increased significantly in the STZ group diabetic rats. Treatment with losartan significantly prevented the raise in cholesterol, creatinine, urea and blood urea nitrogen levels. Creatinine clearance was significantly less in STZ-diabetic rats as compared to control animals and treatment with losartan significantly increased creatinine clearence. Our data suggest a beneficial effect of losartan in STZ - induced nephropathy in rats.     

钙营养对氟的骨骼毒性的影响

用富钙平衡饲料和低钙偏食饲料分别饲养Ｗｉｓｔａｒ大鼠,并经饮水投予氟１００ｍｇ／Ｌ,为期４个月,以研究钙营养对氟的骨骼毒性的影响及其作用机理。     

吡喹酮治疗对血吸虫感染小鼠免疫病理变化的影响

目的 :阐明吡喹酮治疗对血吸虫感染宿主免疫病理的影响。方法 :应用免疫组织化学和图像分析技术 ,观察日本血吸虫感染小鼠在吡喹酮治疗后肝组织内可溶性虫卵抗原 ( SEA)及抗体水平和虫卵肉芽肿的变化。结果 :治疗后 5wk,与对照组相比 ,治疗组减虫率为 98.3% ,平均肝重量和体积均显著减小 ,治愈小鼠的肝表面结节明显减少 ,组织内沉积的虫卵已钙化 ,部分虫卵肉芽肿已呈纤维疤痕样改变 ,对照组肝内仍可见慢性和少量急性虫卵肉芽肿。治疗组肝组织内抗原水平下降 ,而其抗体水平不受影响 ,肝内虫卵肉芽肿的平均直径和面积均较对照组显著缩小 ( P<0 .0 1)。结论 :吡喹酮治疗可使肝组织内 SEA水平下降 ,从而抑制了虫卵肉芽肿的病变 ,但不能逆转已形成的虫卵肉芽肿病变。     

A PRELIMINARY STUDY ON THE EFFECT OF ALPHA-INTERFERON TREATMENT ON THE JOINT INFLAMMATION AND SERUM CALCIUM IN RHEUMATOID ARTHRITIS

A 12-week, double-blind controlled study comparing low dose     

INHIBITORY EFFECT OF SEROTONIN ANTAGONISTS ON GROWTH HORMONE RELEASE IN ACROMEGALIC PATIENTS

We evaluated the effect of the serotonin antagonists cyproheptadine (Cypro) and methysergide (Methy) on growth hormone secretion in six patients with acromegaly. Two days administration of Cypro deceased the plasma GH concentration during oral glucose tolerance tests in four of the six patients evaluated; 2 days administration of Methy reduced the plasma GH levels of only one of the four patients evaluated. The one patient whose palsma GH concentration was lowered by Methy, did not have a decerase in plasma GH concentration after Cypro administration. Acromegalic patients have normal serum serotonin concentration and normal 5-hydroxyindoleacetic acid excretion. If Cypro lowers plasma GH by antagonizing serotonin, our data would suggest that serotoninergic neruonal pathways are important in the regulation of pituitary GH secretion in some patients with acromegaly.     

钙剂加维生素D治疗对糖尿病患者钙代谢的影响

本文报道NIDDM患者在常规治疗的基础上加用钙剂和维生素D治疗后的钙代谢变化。糖尿病患者单纯用常规治疗控制血糖后,负钙平衡不能完全纠正,而加用钙剂和维生素D治疗后,负钙平衡能完全纠正,并且高于正常对照组平衡值(P<0.01)。说明钙剂加维生素D治疗对糖尿病性骨质疏松是有益的。     

EFFECT OF TWO SEROTONIN ANTAGONISTS ON PROLACTIN AND THYROTROPHIN SECRETION IN MAN

The effects of serotoninergic blockade on prolactin and thyrotrophin secretion in man was evaluated by determining the basal and TRH-stimulated serum prolactin and TSH concentrations in normal volunteers before and after a 3 days course of cyproheptadine or methergoline administration. Cyproheptadine, a serotonin antagonist with antihistaminic, anticholinergic and antidopaminergic properties as well, did not affect prolactin secretion, while it reduced the serum TSH response to TRH; methergoline, a specific blocker of central serotonin receptors, decreased basal and TRH-induced serum prolactin levels, without affecting TSH secretion. These results support the existence of serotoninergic stimulatory influences on human prolactin release, while suggesting that human TSH secretion is not modulated by serotoninergic inputs.     

EFFECT OF NICARDIPINE VERSUS ENALAPRIL ON PLASMA ENDOTHELIN-1 IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

We compared the effects of dihydropyridine type Ca channel blocker slow-release nicardipine and angiotensin converting enzyme inhibitor enalapril on plasma endothelin-1 (ET-1) levels in hypertensive type 2 diabetic patients (n = 20). Nicardipine or enalapril was administered for 6 months by a crossover design. Nicardipine and enalapril comparably lowered blood pressure. Enalapril significantly reduced urinary albumin excretion in microalbuminuric patients, whereas nicardipine did not. Urinary β2-microglobulin excretion was significantly increased during nicardipine treatment. However, both drugs significantly reduced plasma ET-1 as compared with pretreatment levels, close to that in healthy control (2.9 ± 0.3 pg/ml in control, 4.8 ± 0.3 pg/ml before treatment, 3.2 ± 0.3 pg/ml during nicardipine vs before treatment p<0.05, 2.9 ± 0.4 pg/ml during enalapril vs before treatment p<0.01). The decrease in plasma ET-1 was significantly correlated with the increase in natriuresis in normoalbuminuric patients treated with enalapril (r=?0.82, p<0.01) but not in those treated with nicardipine. Although nicardipine and enalapril had different renal effects, both drugs equally suppressed plasma ET-1 levels in hypertensive patients with type 2 diabetes.     

血脂康对原发性高脂血症的临床疗效

为研究血脂康的降脂作用强度，对１０８例原发性高脂血症患者，按血脂水平分层配对随机分组，５３例服血脂康，５５例服辛伐他丁作为对照。８周末两组血清总胆固醇（ＴＣ）分别下降２３．０％与２３．３％，低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）分别下降２８．０％与２９．５％，甘油三酯（ＴＧ）分别下降２８．１％与２９．５％。各自与治疗前相比差异均有显著性（Ｐ均＜０．００１），但两组间对比差异无显著性（Ｐ均＞０．０５）。血脂康耐受性好，无明显不良反应。提示血脂康是与辛伐他丁疗效相似的国产高效血脂调节剂。     

卡托普利对高血压病患者红细胞钠和钙离子转运的影响

本文观察了高血压病(EH)患者红细胞膜钠泵、钙泵活性和红细胞内离子浓度的变化,以及卡托普利对其的影响。结果表明,59例EH患者钠泵和钙泵活性显著低于正常人,细胞内钠和钙离子浓度显著高于正常人。其中23例经卡托普利治疗后,钙泵活性升高,细胞内钙离子浓度下降,其升高或减少的程度与血压的下降之间有显著相关性。提示EH患者存在钠和钙离子转运障碍,卡托普利对其有一定影响。     

LONG-TERM TREATMENT OF HYPERPROLACTINAEMIA WITH BROMOCRIPTINE: EFFECT OF DRUG WITHDRAWAL

Fifty-one patients with hyperprolactinaemia (23 with macroadenoma, 23 with microadenoma, and five with idiopathic hyperprolactinaemia) were treated with bromocriptine for 2-12 years (4.9 +/- 2.9 years, mean +/- SD). During therapy, the serum PRL levels were suppressed into the normal range in all but five patients. In these five patients, despite the high circulating PRL, gonadal function returned to normal in three, while in the other two gonadotrophin reserve was impaired even before therapy. Gel chromatography showed that one of these patients had a high proportion of a large molecular weight form of PRL. Twenty-four patients received bromocriptine as the sole method of treatment for over 2 years (3.4 +/- 2.3 years). In five out of the 24 subjects (21%), serum PRL remained normal with no clinical symptoms after prolonged drug withdrawal (1-4 years). Twenty-one patients received radiotherapy in conjunction with bromocriptine therapy. Of these 11 had prior surgery. After a follow-up of 6.0 +/- 3.0 years after radiotherapy, serum PRL remained within the normal range in 6 out of 21 subjects (29%), 1-4 years after bromocriptine withdrawal. One of the patients had impaired GH response to insulin hypoglycaemia developing after radiotherapy. We conclude that prolonged bromocriptine treatment is an effective treatment for prolactinomas.     

冠心病患者皮下注射肝素钙抗凝作用的临床观察

观察１６例冠心病患者皮下注射肝素钙７５００ＩＵ后，对激活全血凝固时间（ＡＣＴ）的影响。分别检测皮下注射前、注射后１ｈ、２ｂ、４ｈ、８ｈ、１２ｈ的ＡＣＴ值。结果显示，注药后１ｈＡＣＴ开始升高，２ｈ达高峰，为注药前的１．３２倍，４～８ｈ有下降趋势，１２ｈ降至注药前水平。静脉滴注肝素钠３天，停药２～４ｈ后再皮下注射肝素钙，其ＡＣＴ值与未先静脉用药者比较无差异；长期小剂量服用阿司匹林，对皮下应用肝素钙后ＡＣＴ值无影响。本研究提示，皮下注射肝素钙７５００ＩＵ／次是安全剂量，无需监测ＡＣＴ。