当归对高血压病患者血浆血栓素及前列环素水平的影响

目的 :探讨当归对高血压病 ( EH)患者血浆血栓素及前列环素的影响。方法 :将 60例 EH患者随机分为 A、B两组 ,各 30例 ,分别给予当归和安慰剂治疗 ,疗程均为 4周。另 60例正常健康人作为对照组。结果 :EH组的血浆血栓素 B2 ( Tx B2 )明显高于对照组 ,血浆 6-酮 -前列腺素 ( 6- keto-PGF1α)则显著降低。A组治疗后血浆 Tx B2 水平降低 ,6- keto- PGF1α升高 ( P<0 .0 1)。B组治疗前后无明显变化。结论 :当归能提高 EH患者血浆 6- keto- PGF1α,降低 Tx B2 。     

Kinins, nitric oxide, and the hypotensive effect of captopril and ramiprilat in hypertension.

We investigated the role of kinins in the acute depressor effect of captopril and ramiprilat in spontaneously hypertensive rats. Since the vasodepressor action of kinins may be linked to the generation of prostaglandins and endothelium-derived relaxing factors, we also investigated the role of prostaglandins and nitric oxide in the blood pressure reduction caused by angiotensin converting enzyme inhibitors. To this end, we contrasted the hypotensive effects of captopril (10 mg/kg i.v.), ramiprilat (2 mg/kg i.v.), and the angiotensin II antagonist DuP 753 (30 mg/kg i.v.) in spontaneously hypertensive rats with and without pretreatment with a kinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid) (200 micrograms/kg/min i.v.), an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine) (15 mg/kg + 10 mg/kg/hr i.v.), or an inhibitor of prostaglandin synthesis (indomethacin) (10 mg/kg i.v.). The kinin antagonist did not affect blood pressure in spontaneously hypertensive rats but did attenuate the hypotensive effect of captopril and ramiprilat; the kinin antagonist did not minimize the depressor action of DuP 753. The nitric oxide synthesis inhibitor increased blood pressure in spontaneously hypertensive rats and attenuated the hypotensive effect of captopril, ramiprilat, and DuP 753, but it did not impede the hypotensive effect of sodium nitroprusside. Pretreatment of hypertensive rats with indomethacin did not modify the acute hypotensive effect of ramiprilat or captopril. These data suggest a contribution of endogenous kinins and nitric oxide to the acute antihypertensive effect of captopril and ramiprilat in spontaneously hypertensive rats and of nitric oxide to the hypotensive effect of DuP 753.     

Amlodipine and captopril in moderate-severe essential hypertension

The therapeutic usefulness of adding once-daily amlodipine (10 mg) for four weeks in moderate-severe hypertensive patients uncontrolled on low dose captopril (25 mg twice daily) alone was studied in 29 patients in a double-blind, placebo-controlled two-way crossover comparison. Once daily amlodipine was shown to be an effective antihypertensive drug when combined with captopril. The amlodipine minus placebo differences in mean changes from captopril baseline values were: -18/-12 mmHg and -20/-12 mmHg for supine and standing systolic/diastolic pressures (P less than 0.001 for all four pressure variables). The combination was well tolerated, and no patient discontinued therapy. Five patients experienced ankle oedema and four patients reported flushing while receiving amlodipine/captopril.     

卡托普利治疗有合并症的老年原发性高血压的效果

目的:观察卡托普利治疗有合并症的老年原发性高血压的临床疗效,并评价其安全性。方法:选择我院收治的116例老年原发性高血压伴有脂代谢紊乱、糖尿病等合并症的患者,按照随机数字表法均分为阿替洛尔对照组和卡托普利组(在阿替洛尔对照组基础上加用卡托普利)。观察两组患者治疗前、后血压、心率、空腹血糖、血脂变化情况,评价其临床疗效和不良反应。结果:治疗后,卡托普利组总有效率明显高于阿替洛尔对照组(98.28%比87.93%,P0.05);与阿替洛尔对照组比较,卡托普利组患者血压[(131.20±11.02/82.01±6.75)mmHg比(115.62±10.27/75.68±5.21)mmHg]、心率[(65.14±6.32)次/min比(57.21±4.02)次/min]、空腹血糖[(4.75±1.36)mmol比(3.65±1.24)mmol]、总胆固醇[(2.69±0.58)mmol/L比(2.10±0.41)mmol/L]、甘油三酯[(0.96±0.41)mmol/L比(0.72±0.35)mmol/L]、低密度脂蛋白胆固醇[(1.95±0.57)mmol/L比(1.71±0.40)mmol/L]水平降低更显著(P0.05或0.01);两组患者均未发生明显不良反应。结论:卡托普利治疗有合并症的老年原发性高血压的疗效比阿替洛尔更佳,且无不良反应,值得推广应用。     

Absence of effects of ketanserin on renal prostacyclin and thromboxane A2 in essential hypertension

The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane.     

Long-term efficacy of captopril in renovascular and essential hypertension

Captopril was used in primary and long-term treatment of 40 treatment-resistant hypertensive patients. Of these, 21 had renovascular hypertension, seven unilateral and fourteen bilateral, and 19 had essential hypertension, 10 with high-renin and 9 with normal-renin profiles. All patients were off treatment when started on captopril therapy and were treated for at least 12 months, on the average for more than 2 years. The strategy of systematic drug withdrawal used to find the lowest effective dose of captopril led to average doses of 150 to 300 mg/day. A diuretic agent was added in 17 of the 40 patients when diastolic pressure remained greater than 105 mm Hg and a beta-adrenergic blocking agent was added for tachycardia or additional pressure control in 16 patients. Captopril alone was effective in 14 of the 40 patients. In all groups, mean supine and standing blood pressure levels were maintained at less than 140/90 mm Hg without evidence of decreased effectiveness over time. Control and treatment systolic pressures were higher in patients older than 50 years. For patients of all ages, systolic but not diastolic pressure during captopril treatment was higher in the supine position than standing. Plasma renin activity remained significantly elevated over time and aldosterone excretion usually decreased despite concurrent diuretic therapy. Captopril alone or in combination with a diuretic or beta-adrenergic blocking agent is effective in long-term treatment of drug-resistant renovascular and essential hypertension.     

Modification of arterial baroreflexes by captopril in essential hypertension

Captopril lowers blood pressure without increasing heart rate and plasma norepinephrine, which suggests that this drug may potentiate arterial baroreflexes. In eight subjects with untreated essential hypertension, blood pressure was monitored intraarterially and the effects of baroreceptor stimulation or deactivation were assessed by measuring (1) the slopes of the relations between increase or reduction in systolic pressure (intravenous phenylephrine or nitroglycerin) and the resulting lengthening or shortening in R-R interval, and (2) the increase or decrease in mean arterial pressure induced by increasing and decreasing carotid transmural pressure (neck chamber). The measurements were made before and after a hypotensive oral dose of captopril (50 mg). Before captopril, the slopes of the R-R interval changes with increase and reduction in systolic pressure were 8 and 4 ms/mm Hg, respectively. The slopes of the mean arterial pressure changes with increase and reduction in carotid transmural pressure were 0.51 and 0.40 mm Hg, respectively. After captopril, the responses to baroreceptor stimulation were unaltered but those to baroreceptor deactivation were augmented. The presser and heart rate responses to hand-grip and cold exposure were unchanged by captopril.Administration of captopril is accompanied by a baroreflex potentiation which involves the lower portion of the stimulus-response curve of the reflex. This phenomenon (which may originate at the afferent baroreceptor fibers or centrally) may avoid a reduction in the tonic baroreflex influence during captopril-induced hypotension, thus contributing to the hemodynamic effects of the drug.     

Role for thromboxane receptors in angiotensin-II-induced hypertension

To evaluate the role of thromboxane in hypertension and its complications, we studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin-II-dependent model of hypertension. To determine whether genetic background might alter the physiological actions of the TP receptor, we studied two lines of TP knockout (Tp-/-) mice with distinct genetic backgrounds (C57BL/6 and BALB/c). During chronic angiotensin II infusion (1000 ng/kg per minute x 28 days by subcutaneous osmotic pump), TP deficiency prevented mortality in the C57BL/6 background but not in the BALB/c strain. Chronic angiotensin II infusion also caused a rapid and significant increase in blood pressure in wild-type (WT) C57BL/6 and BALB/c animals, which was significantly attenuated in Tp-/- mice on either background. After 28 days of infusion, cardiac hypertrophy only occurred in the C57BL/6 strain: heart/body weight ratio increased by 57%+/-8% in WT mice compared with 17%+/-6.5% for the Tp-/- mice (P<0.01). Chronic angiotensin II infusion caused albuminuria only in the C57BL/6 strain, and TP deficiency did not alter its development. Cyclooxygenase-1 knockout mice also had attenuated blood pressure increase during chronic angiotensin II infusion, suggesting that cyclooxygenase-1 metabolites are involved in angiotensin-II-dependent hypertension. Thus, on the C57BL/6 background, TP receptors contribute to cardiac hypertrophy but not proteinuria. However, irrespective of genetic background, the TP receptor makes a robust contribution to the pathogenesis of angiotensin II-dependent hypertension.     

The antihypertensive effect of captopril in essential hypertension: relationship to prostaglandins and the kallikrein-kinin system

Two groups, each with nine essential hypertensive patients, were maintained on 10 mmol sodium daily over 14-17 days and treated in this sequence: placebo; captopril (25 or 50 mg given thrice daily) or indomethacin (50 mg given thrice daily) alone; captopril plus indomethacin, and (4) captopril alone. The initial fall in mean blood pressure induced by captopril (118 +/- 1 to 102 +/- 1 mmHg) was unaffected by the addition of indomethacin. However, if indomethacin treatment preceded captopril, the antihypertensive effect was attenuated (116 +/- 4 to 109 +/- 4), and was associated with significant reductions in urinary prostaglandin and kinin excretion. Addition of captopril to indomethacin returned kinin excretion to placebo levels but did not affect indomethacin-induced reduction in prostaglandin excretion. Captopril alone stimulated plasma renin activity (PRA) fivefold; aldosterone excretion was lowered by 25% and further reduced by indomethacin. Thus, when captopril and indomethacin are administered together, the order of administration is critical to the antihypertensive effect of captopril.     

Twenty-four hour profile of the hypotensive action of felodipine in essential hypertension

Summary Felodipine, 10 mg twice daily, and placebo were administered for 5 weeks to ten untreated essential hypertensives in a double-blind, random-order, crossover study. At the end of each phase patients were assessed by 36 hours of continuous intraarterial blood pressure recordings, both during normal activities and specified activities. Patients were also assessed by 36-hour Holter analysis, maximal exercise testing, radionuclide cardiac scan, and measurement of endogenous creatinine clearance and 2-hourly vasoactive hormones. Arterial pressure was significantly reduced by felodipine, with mean falls in blood pressure of 25.1 mmHg and 12.5 mmHg (systolic and diastolic, respectively) over 24 hours. Blood pressure was reduced by felodipine during moderate and maximal exercise and mental stress. There were no significant changes in heart rate, exercise capacity, ventricular ectopy, endogenous creatinine clearance, or vasoactive hormones.     

A double-blind comparison of bisoprolol and captopril for treatment of essential hypertension in the elderly

Summary The aim of the study was to compare the antihypertensive efficacy and safety of a new beta blocker with high beta₁ selectivity, bisoprolol, with captopril in 28 elderly patients, aged over 65 years, with mild-to-moderate essential hypertension (WHO classes I and II). After a placebo run-in period of 4 weeks, the patients were randomly allocated to receive bisoprolol (5 mg od) or captopril (25 mg bid) doubledummy technique) for 6 weeks, according to a crossover double-blind design, with a 4-week washout period between the two active treatments. The doses were doubled after 2 weeks if the supine blood pressure was >160/95 mmHg. In basal conditions and after 2, 4, and 6 weeks of each treatment, the blood pressure and heart rate were assessed both in the supine and erect positions. At the same time, the side effects and quality of life were investigated by a checklist and a selfassessment questionnaire. Standard laboratory tests and a resting ECG tracing were performed before and after each active treatment. The data from 24 patients (4 dropouts) showed a significant antihypertensive effect of both treatments (p<0.01) with a reduction of diastolic blood pressure to values 95 mmHg in 75% (18/24) of the patients treated with bisoprolol and in 83.3% (20/24) of those treated with captopril, without significant differences between the two drugs. Bisoprolol also produces a marked but symptom-free reduction of heart rate compared with captopril (p<0.05). Neither the beta blocker nor the ACE inhibitor caused important side effects or worsening of the patients' quality of life, and no changes in laboratory tests and ECG tracings were observed. In conclusion, bisoprolol demonstrated antihypertensive action and tolerability comparable with captopril, and it is a suitable treatment in elderly hypertensive patients.     

Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension

To determine whether prostaglandins contribute to the depressor response to the converting enzyme inhibitor, captopril, we measured the plasma prostaglandin levels by radioimmunoassy before and after captopril administration, and then examined the effect of prostaglandin synthetase inhibition on captopril's antihypertensive effect. When a single oral captopril dose (25-100 mg) was given to 31 sodium-restricted patients with essential hypertension, the levels of the stable transformation product of prostacyclin remained unmeasurable and that of thromboxane A2 did not change, while the metabolite of PGE2 (PGE-M) increased by 53% (34 +/- 4pg/ml pre-captopril, 52 +/- 5 pg/ml after; p less than 0.001). As expected, blood pressure (BP) and angiotension II (AII levels fell, and kinin levels rose (all changes p less than 0.001). We then blocked prostaglandin synthesis in 18 of these subjects for 24 hours with either indomethacin (n = 10) or aspirin (n = 8) before repeating the captopril dose, to assess the importance of these PGE-M increments. The PGE-M responses to captopril were effectively blocked in nine of 10 subjects receiving indomethacin and four of eight receiving aspirin. In these 13 patients, the depressor response to captopril was significantly blunted (-20 +/- 3mm Hg pre-synthetase inhibition vs - 13 +/- 2 mm Hg post; p less than 0.05). When these agents did not block the PGE-M response to captopril, the BP response was also unchanged (-15 +/- 4mm Hg pre, -18 +/- 5mm Hg post). Neither indomethacin nor aspirin changed the AII or kinin responses to captopril. We conclude that the prostaglandins may be important mediators of captopril's antihypertensive effect in the sodium-restricted state.     

Role of methylglyoxal in essential hypertension

Altered glucose metabolism due to insulin resistance is a common feature of essential hypertension in humans and in animal models. Elevated endogenous aldehydes in genetic (spontaneously hypertensive rats) and acquired (fructose-induced hypertensive rats) models of essential hypertension may be due to increased production of the reactive aldehyde methylglyoxal, resulting from altered glucose metabolism. Excess methylglyoxal binds sulfhydryl groups of membrane proteins, altering calcium channels and increasing cytosolic free Ca(2+) and blood pressure. It has been demonstrated that methylglyoxal, when given in drinking water to Wistar-Kyoto rats, leads to an increase in kidney aldehyde conjugates, cytosolic free Ca(2+) concentration, decreased serum nitric oxide, renal vascular hyperplasia and hypertension. N-acetylcysteine (NAC) in the diet of these animals prevented hypertension and associated biochemical and morphological changes. NAC normalizes blood pressure by directly binding to excess methylglyoxal, thus normalizing Ca(2+) channels, cytosolic Ca(2+) and nitric oxide. NAC also leads to increased levels of tissue glutathione, a storage form of cysteine. Glutathione acts as a cofactor in the enzymatic catabolism of methylglyoxal. Cysteine and other antioxidants, such as vitamins B(6), C and E, and lipoic acid, prevented hypertension and associated biochemical and morphological changes in both genetic and acquired rat models of hypertension. The antihypertensive effect of dietary antioxidants may be due to an increase in tissue cysteine and glutathione, which improves glucose metabolism and decreases tissue methylglyoxal. A diet rich in these antioxidants may be effective in preventing and controlling hypertension in humans.     

Mechanisms of the hypotensive effect of psychorelaxation therapy in hypertension

An evaluation of the effect of mental relaxation treatment on endogenous opioid activity and vascular reactivity in 20 patients with labile essential hypertension has demonstrated that mental relaxation treatment results in a significantly greater drop in arterial BP, as compared to pharmacologic placebo, and is associated with the improvement of the patients' psychological status, lesser psychophysiologic and vascular reactivity, and a smaller beta-endorphin increment under emotional stress.