原发性高血压患者红细胞抗高血压因子对高血压大鼠血压的影响

本工作观察了原发性高血压患者 (EHS) 红细胞抗高血压因子(AHF)对自发性高血压大鼠(SHR)和肾性高血压大鼠(RHR)及正常血压的 wistar Kyoto(WKY)大鼠和 wistar 大鼠的收缩压(SBP)和舒张压(DBP)的影响。结果如下:(1)从腹腔一次注入 AHF(1.6mg/kg体重),可明显降低 SHR 和 RHR 的 SBP。给 AHF10min 后,SHR 的 SBP 平均降低34.0 mmHg,至3h 恢复;RHR 在注射 AHF 后24h,SBP 平均降低92.5mmHg,且持续时间较长,至第九天仍维持在低水平。(2)从股静脉一次推注 AHF(0.8 mg/kg体重)后,SHR 和 RHR的 SBP 和 DBP 均有显著性降低,且对 RHR 作用时间较 SHR 长,对 DBP 作用时间较 SBP长。给 AHF 后12 min,SHR 的 SBP 和 DBP 分别降低42.8和48.2 mmHg;RHR 在给AHF 后25 min,SBP 和 DBP 分别降低38.3和42.5 mmHg;AHF 后5min,wistar大鼠 DBP 由96.7±12.9mmHg 降到 83.3±11.7 mmHg(P<0.05),而 SBP 无明显变化。AHF 的降压作用具有剂量依赖性。(3)AHF 可拮抗去甲肾上腺素对 Wistar 大鼠的升压作用。     

原发性高血压患者红细胞中存在抗高血压因子

本研究利用热处理和Sephadex G-150凝胶过滤层析等方法,从原发性高血压病患者(EHS)红细胞中部分纯化了抗高血压因子(AHF)。AHF具有热稳定性,分子量大于6kDa;能明显降低卒中易感型自发性高血压大鼠(SHR_(sp))血压,腹腔一次注入AHF(1.6mg/kg)30min后,SHR_(sp)收缩压从原来的27.6±0.7kPa降低到21.4±0.8kPa(p<0.001),4h后收缩压恢复至原水平。AHF能显著抑制自发性高血压大鼠(SHR)和肾性高血压大鼠(RHR)主动脉(A)及肠系膜动脉(MA)血管平滑肌(VSM)Ca~(2 )内流。且对MA Ca~(2 )内流的抑制作用强于A。以上结果表明:EHS红细胞中存在AHF,能显著降低高血压大鼠血压,其降压机制可能与其抑制VSM特别是小动脉VSM Ca~(2 )内流有关。     

红细胞抗高血压因子降压作用的进一步研究

我们曾报道原发性高血压患者(EHS)红细胞抗高血压因子(AHF)具有缓慢而持久的降压作用。本工作表明,AHF对卒中易感型自发性高血压大鼠(SHRsp)还具有快速短暂的降压作用,注射AHF后10—30s,SHRsp收缩压从原水平的26.8±1.7kPa降至20.1±1.5kPa(P<0.001)。正常人和大鼠红细胞AHF的降压作用明显强于EHS和高血压大鼠AHF。此外我们还发现EHS血浆中存在升压物质。以上结果提示,AHF缺乏和升压物质含量相对较高可能是原发性高血压发病的一个重要原因。     

红细胞抗高血压因子舒血管作用机制的研究

本实验研究了从Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠红细胞中提取的抗高血压因子（ａｎｔｉｈｙｐｅｒｔｅｎｓｉｖｅｆａｃｔｏｒ,ＡＨＦ）对苯肾上腺素引起的Ｗｉｓｔａｒ大鼠胸主动脉螺旋条预收缩的舒张作用。结果表明：ＡＨＦ对主动脉条的舒张呈内皮与剂量依赖性。左旋硝基精氨酸与美蓝均可阻断ＡＨＦ的舒血管作用,而铜锌超氧化物歧化酶对ＡＨＦ的舒血管效应有促进作用。提示ＡＨＦ是通过刺激内皮细胞产生一氧化氨或其类似物,从而激活血管平滑肌细胞内可溶性鸟苷酸环化酶这一途径引起血管舒张的。     

原发性高血压患者和高血压大鼠红细胞形态的电镜观察

原发性高血压患者和高血压大鼠红细胞形态的电镜观察ＥＬＥＣＴＲＯＮＭＩＣＲＯＳＣＯＰＩＣＳＴＵＤＹＯＮＥＲＹＴＨＲＯＣＹＴＥＳＨＡＰＥＩＮＥＳＳＥＮＴＩＡＬＨＹＰＥＲＴＥＮＳＩＶＥＰＡＴＩＥＮＴＳＡＮＤＨＹＰＥＲＴＥＮＳＩＶＥＲＡＴＳ关键词高血压患者高...     

自发性高血压大鼠血浆高血压因子的升压机制

自发性高血压大鼠血浆高血压因子的升压机制赵睿珊,胡晓东,王辅才,吴代英（河北省医学科学院实验医学研究所石家庄０５００２１）本工作研究在自发性高血压大鼠（ＳＨＲ）的血浆中存在的一种具有独特性质的高血压因子（ＨＦ）的作用,从而探讨高血压发病的原因、机制和...     

交感神经损毁术对自发性高血压大鼠血压和红细胞Na~＋外流动力学的影响

本实验研究了皮下注射６—羟多巴胺（６—ＯＨＤＡ）施行交感神经损毁术对成年自发性高血压大鼠（ＳＨＲ）血压和红细胞Ｎａ＋外流动力学的影响。结果表明,在幼年期施行交感神经损毁术的ＳＨＲ血压显著低于未损毁组,同时红细胞Ｎａ泵驱动的的Ｎａ＋外流最大速率显著下降、Ｎａ＋－Ｋ＋外向协同转运系统的单位活性升高。三者均接近ＷＫＹ大鼠的测定值。相反,损毁成年ＳＨＲ交感神经不影响上述两个动力学参数,血压也未见明显改变。此外,不论幼年或成年期注射６—ＯＨＤＡ均可降低Ｎａ＋—Ｌｉ＋对向转运系统驱动的Ｎａ＋外流最大速率。上述结果提示,在ＳＨＲ早期发育过程中,交感神经营养因子可能降低Ｎａ＋—Ｋ＋外向协同转运活性,继而刺激Ｎａ泵代偿功能增强。这种现象可能同时存在于ＳＨＲ动脉平滑肌,因而是高血压产生的一个原因。关于交感神经损毁术后ＳＨＲ红细胞Ｎａ＋—Ｌｉ＋对向转运最大速率下降的机制尚不清楚,但与交感神经早期营养作用的消除无关。     

Effects of exercise training on plasma catecholamines and blood pressure in labile hypertensive subjects

Plasma catecholamine concentrations (norepinephrine, NE; epinephrine, E) were measured along with heart rate (HR) and blood pressure (BP) at rest in supine (20 min) and standing (10 min) positions and in response to cycle ergometer exercise (5 min; 60% estimated maximal aerobic power) in 12 hypertensive patients before and after 20 weeks of aerobic training on cycle ergometer (six males, one female) or by jogging (five males). In a control group of labile hypertensive patients (five males, two females), estimated maximal aerobic power as well as HR and BP at rest in the supine and standing positions and in response to exercise were not modified from the first to the second evaluation (43 +/- 4 vs 43 +/- 5 ml.kg-1.min-1). In comparison estimated maximal aerobic power significantly increased in both training groups (cycle: 38 +/- 4 to 43 +/- 4; jogging: 38 +/- 3 to 46 +/- 4 ml.kg-1.min-1). However HR and BP were not modified following training, except for small reductions in systolic (18.9 to 18 kPa: 142 to 135 mmHg) and diastolic pressures (13.3 to 12 kPa: 100 to 90 mmHg) (p less than 0.05) at standing rest in the cycle group.(ABSTRACT TRUNCATED AT 250 WORDS)     

游泳训练对高血压大鼠血压及血栓前状态分子的影响

目的:观察10周游泳训练对自发性高血压大鼠(SHR)血压及血栓前状态分子血管性血友病因子(vWF)、组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物(PAI-1)的影响。方法:选取10周龄雄性SHR(18只),随机分为对照组(8只)和训练组(10只),SHR训练组进行5次/周,每次60 min,共持续10周的无负重游泳训练,期间每2周测定大鼠血压。10周训练后,分别测定两组SHR血小板聚集率、血浆vWF、t-PA和PAI-1。结果:与对照组相比,训练组SHR经4周游泳训练后,血压显著下降(P<0.05),经10周游泳训练后,血压、血小板聚集率、血浆vWF水平、PAI-1活性显著降低(P<0.01),血浆t-PA活性显著提高(P<0.01)。结论:适宜游泳训练能有效平抑(或改善) SHR的血压,坚持4周训练即可产生显著的作用,还可明显改善SHR血栓前状态,预防高血压血栓性并发症。     

Vasoactive humoral systems and sodium transport in erythrocytes of normotensive offsprings of essential hypertensive subjects

Urinary excretion of sodium, potassium and some hormones influencing their transport was investigated before and after i.v. furosemide administration in 10 offsprings of normotensive subjects who had a normal Na(+)-K+ cotransport activity and in 26 normotensive men with a positive family history of essential hypertension. The latter group was divided into two subgroups with regard to the activity of red cell Na(+)-K+ cotransport. The Co[-] subjects with a decreased Na(+)-K+ cotransport activity had lower urinary excretion of sodium and vasodilators (kallikrein, dopamine, PGE2 and prostacyclin) after furosemide administration. The urinary excretion of vasopressor factors (PGF2 alpha, thromboxane) was unchanged as compared with that in the control group. There was a significant correlation between Na(+)-K+ cotransport activity and kallikrein excretion. These results suggest a deficit in the secretion of renal substances with vasodilating or natriuretic effects in Co[-] subjects. This could negatively affect their sodium excretion.     

Effects of praeruptorin C on blood pressure and expression of phospholamban in spontaneously hypertensive rats

BackgroundThe traditional Chinese medicine Praeruptorin c (Pra-c) has many physiological and pharmacological effects, including antagonistic effects on blood pressure and calcium levels, maintenance of cellular calcium homeostasis, and improved cardiac systolic and diastolic function. It is potentially a novel and versatile drug for the treatment and prevention of cardiovascular diseases.ObjectiveTo explore the possible impact of Pra-c on blood pressure in SHR and its mechanism of action.Materials and methodsTwenty SHR were randomly divided into a Pra-c group [Pra-c was administered intragastrically, 20 mg kg⁻¹ d⁻¹, n = 10] or an untreated control group (n = 10), containing 10 age-matched SD rats. Each group of rats was followed for 8 weeks. Before and during the treatment, tail artery systolic blood pressure was measured using a tail-cuff every 2 weeks. After 8 weeks, the rats were sacrificed and RNA was extracted from homogenates of cardiac tissue. Tissue from the left ventricle was fixed, sectioned and H&E stained to assess possible changes in myocardial cell structure and morphology. Semi-quantitative RT-PCR was used to assess changes in phospholamban gene expression in treated and untreated rats.ResultsSHR treated with Pra-c for 8 weeks had a lower systolic pressure than untreated SHR (p < 0.05), two measures of cardiac damage, the heart mass index and left ventricle mass index (HMI and LVMI, respectively) were improved, and the level of PLB mRNA expression was lower in the untreated SHR group (p < 0.05).Discussion and conclusionWith continuous hypertension, SHR gradually formed or developed cardiac hypertrophy and fibrosis. Pra-c had a clear effect on blood pressure in SHR, and reversed SHR ventricular remodeling by upregulating the gene expression of sarcoplasmic reticulum PLB.     

Effects of minoxidil on blood pressure and cardiac hypertrophy in two-kidney, one-clip hypertensive rats

Rats made severely hypertensive by renal arterial clipping were treated for 24 days with the arterial vasodilator minoxidil (40, 80, and 120 mg/L drinking water). In all three treated groups of animals, blood pressure initially decreased markedly and to a similar extent. Subsequently partial tolerance developed to the antihypertensive effects of minoxidil. All three doses induced hypertrophy of the right ventricle to a similar degree. In contrast, the hypertension-induced hypertrophy of the left ventricle was further increased in a dose-dependent fashion by minoxidil.     

Effects of moderate physical training on blood pressure variability and hemodynamic pattern in mildly hypertensive subjects.

The objective of our study was to compare the cardiovascular effects of moderate exercise training in healthy young (NTS, n=18, 22.9+/-0.44 years) and in hypertensive human subjects (HTS, n=30, 23+/-1.1). The VO(2max) did not significantly differ between groups. HTS of systolic blood pressure (SBP) 148+/-3.6 mmHg and diastolic blood pressure(DBP) 88+/-2.2 mmHg, and NTS of SBP: 128.8 +/- 4 mmHg and DBP: 72 +/- 2.9 mmHg were submitted to moderate dynamic exercise training, at about 50% VO(2max) 3 times per week for one hour, over 3 months. VO(2max) was measured by Astrand's test. Arterial blood pressure was measured with Finapres technique, the stroke volume, cardiac output and arm blood flow were assessed by impedance reography. Variability of SBP and pulse interval values (PI) were estimated by computing the variance and power spectra according to FFT algorithm. After training period significant improvements in VO(2max) were observed in NTS- by 1.92 +/-0.76 and in HTS by 3+/-0.68 ml/kg/min). In HTS significantly decreased: SBP by 19 +/-2.9 mmHg, in DBP by 10.7+/-2 mmHg total peripheral resistance (TPR) by 0.28 +/-0.05 TPR units. The pretraining value of low frequency component power spectra SBP (LF(SPB)) was significantly greater in HTS, compared to NTS. PI variance was lower in HTS, compared to NTS. After physical training, in HTS PI variance increased suggesting a decrease in frequency modulated sympathetic activity and increase in vagal modulation of heart rate in mild hypertension. A major finding of the study is the significant decrease of resting low frequency component SBP power spectrum after training in HTS. The value of LF(SPB) in trained hypertensive subjects normalized to the resting level of LF(SPB) in NTS. Our findings suggest that antihypertensive hemodynamic effects of moderate dynamic physical training are associated with readjustment of the autonomic cardiovascular control system.     

Administration-time-dependent effects of doxazosin GITS on ambulatory blood pressure of hypertensive subjects

Previous studies have shown that a single nighttime dose of standard doxazosin, an alpha-adrenergic antagonist, reduces blood pressure (BP) throughout the 24 h. We investigated the administration-time-dependent effects of the new doxazosin gastrointestinal therapeutic system (GITS) formulation. We studied 91 subjects (49 men and 42 women), 56.7+/-11.2 (mean+/-SD) yrs of age with grade 1-2 essential hypertension; 39 patients had been previously untreated, and the remaining 52 had been treated with two antihypertensive medications with inadequate control of their hypertension. The subjects of the two groups, the monotherapy and polytherapy groups, respectively, were randomly assigned to receive the single daily dose of doxazosin GITS (4 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours just before and after 3 months of treatment. After 3 months of doxazosin GITS therapy upon awakening, there was a small and nonstatistically significant reduction in BP (1.8 and 3.2mm Hg in the 24 h mean of systolic and diastolic BP in monotherapy; 2.2 and 1.9mm Hg in polytherapy), mainly because of absence of any effect on nocturnal BP. The 24 h mean BP reduction was larger and statistically significant (6.9 and 5.9 mm for systolic and diastolic BP, respectively, in monotherapy; 5.3 and 4.5 mm Hg in polytherapy) when doxazosin GITS was scheduled at bedtime. This BP-lowering effect was similar during both the day and nighttime hours. Doxazosin GITS ingested daily on awakening failed to provide full 24h therapeutic coverage. Bedtime dosing with doxazosin GITS, however, significantly reduced BP throughout the 24h both when used as a monotherapy and when used in combination with other antihypertensive pharmacotherapy. Knowledge of the chronopharmacology of doxazosin GITS is key to optimizing the efficiency of its BP-lowering effect, and this must be taken into consideration when prescribing this medication to patients.     

Effect of diphenylhydantoin on blood pressure of spontaneously hypertensive rats

Diphenylhydantoin (DPH) has been shown to elicit direct peripheral vasodilatory effects in anaesthetised animals. Since spontaneously hypertensive (SH) rats exhibit many features similar to human essential hypertension, the effect of DPH on blood pressure of these rats was studied. DPH given orally for 5 days elicited dose-dependent fall in systolic blood pressure in conscious SH rats. In addition, repeated administrations of DPH increased the noradrenaline concentration in the hypothalamus. These results suggest that the central noradrenergic mechanisms might be involved in the hypotensive action of DPH in SH rats, probably at the supramedullary level.