EFFECT OF ANTIHYPERTENSIVE THERAPY ON THE CARDIOVASCULAR AMPLIFIERS

1. In established chronic hypertension the amplifier properties of vessels and heart contribute about 70% to the maintenance of the elevated blood pressure (BP). Recent studies in spontaneously hypertensive rats (SHR) suggest that the structural changes occur very early and their amplifier properties may be critical for the development of hypertension. 2. In patients with primary hypertension, the greater the regression of cardiac and vascular hypertrophy, the slower the subsequent redevelopment of hypertension. Following regression of hypertrophy, the antihypertensive action of moderate regular exercise can maintain BP in the normal range in a proportion of patients. 3. Early treatment of SHR with enalapril greatly reduces the subsequent 'steady-state' BP in SHR. This produces virtually complete regression of vascular hypertrophy, but somewhat lesser degrees of regression of cardiac hypertrophy. 4. These studies serve as models for primary and secondary prevention of hypertension. A strategy based on intermittent drug and non-pharmacological therapy in man may contribute to the secondary prevention of atherosclerosis, in view of the adverse effects on lipid profiles of many antihypertensive drugs.     

厄贝沙坦治疗原发性高血压的临床疗效和靶器官保护

目的评价厄贝沙坦治疗原发性高血压的临床疗效及其对原发性高血压左心室肥厚(LVH)的逆转作用以及对肾功能的保护作用。方法 100例确诊为高血压病患者服用厄贝沙坦150 mg,每天1次,每周随访1次,治疗12周,监测治疗前及治疗中24 h动态血压水平及肾功能指标。用超声心动图测量LVH患者左心室肥厚的改善情况。结果厄贝沙坦治疗后,患者24 h平均收缩压及舒张压、日间及夜间收缩压及舒张压均有明显下降(P<0.01),血及尿β2-MG明显减少(P<0.01)。经厄贝沙坦治疗后左心室重量(left ventricular hypertraphy,LVMI)明显下降(P<0.01)。结论厄贝沙坦对原发性高血压患者有良好的平稳降压效果,对原发性高血压患者的LVH有逆转作用,且对其肾功能有良好的保护作用。     

缬沙坦对轻中度高血压患者疗效及左室肥厚的影响

目的探讨缬沙坦治疗轻中度原发性高血压病疗效及对左室肥厚的逆转作用。方法门诊确诊40例轻中度高血压病患者在停服各种心血管活性药物2周后服用缬沙坦（80mg／d）4周。所有患者在用药前及治疗后4周末复查动态血压及心脏超声。结果4周末24h收缩压、舒张压,白昼及夜间收缩压、舒张压,收缩压及舒张压负荷均显著降低,P〈0．05。左室质量指数较治疗前降低,P〈0．05。结论缬沙坦对轻中度高血压病患者有明显降压效果。并且可在短期内逆转左室肥厚。     

洛沙坦抗高血压及左室肥厚的疗效观察

目的 :观察血管紧张素 受体拮抗剂—洛沙坦的降压效果及对高血压病合并左室肥厚的影响。方法 :4 6例合并左室肥厚的 期高血压病患者服用洛沙坦 5 0 mg/ d,观察其血压的变化及治疗前和 6个月后左室质量 (L VM)。结果 :用洛沙坦后 4 d～ 6d血压开始下降 ,2周血压趋向正常 ,4周血压继续缓慢下降 ,6周时达到最大降压效果。 L VM在 12周时无明显变化。 2 4周表现轻度 L VM减少。结论 :洛沙坦是抗高血压的一个有效治疗药物 ,对左心室肥厚有轻度逆转作用     

EVIDENCE FOR A ROLE FOR THE CARDIOVASCULAR AMPLIFIERS IN HUMAN PRIMARY HYPERTENSION

1. Hypertrophy of vascular and cardiac smooth muscle is present in human primary hypertension. The amplifier properties associated with hypertrophy play a major role in maintaining hypertension. 2. Long-term antihypertensive drug therapy causes substantial regression of the structural changes, assessed by the non-autonomic component of vascular resistance, and by left ventricular mass. The latter occurs more slowly. 3. The more complete the reversal of left ventricular hypertrophy, the more slowly hypertension redevelops if long-term antihypertensive therapy is discontinued. 4. Subjects who redevelop hypertension more rapidly tend to have higher cardiac output, suggesting that the cardiac amplifier may play a role in the pathogenesis. 5. Studies of small arteries and of veins from patients with primary hypertension suggest that there may be a general disturbance of vascular smooth muscle function, independent of the mechanical effects of elevated systemic blood pressure.     

坎地沙坦对原发性高血压患者左心室肥厚的作用

目的研究坎地沙坦对原发性高血压（EH）患者的降压作用和对左室肥厚（LVH）的影响。方法选择52例EH患者,其中有LVH者20例,1：2服坎地沙坦8～16mg／d,为期半年。观察血压、不良反应,治疗前后测血脂、血糖和肝肾功能,并作二维超声心动图检测,采用自身前后对照的实验方法。结果EH患者经坎地沙坦治疗后收缩压、舒张压显著下降（P〈0．01）,其中LVH者治疗后左心室舒张末期内径及左室重量均明显下降（P〈0．05）,舒张末期左室后壁厚度、室间隔厚度及左室重量指数下降更明显（P〈0．01）。结论坎地沙坦治疗EH安全、有效,并且可逆转LVH。     

THE EFFECT OF KETANSERIN IN ESSENTIAL HYPERTENSION

1. Ketanserin, a 5HT₂-receptor blocking drug was given to 17 patients with essential hypertension. 2. Satisfactory control was achieved in 13 patients. 3. Control was not as satisfactory when given once daily. 4. There was no rebound effect when the drug was ceased. 5. Side-effects were few. 6. Ketanserin was a satisfactory drug to reduce blood pressure in patients with moderate hypertension.     

VASCULAR SMOOTH MUSCLE POLYPLOIDY IN THE DEVELOPMENT AND REGRESSION OF HYPERTENSION

1. Two groups of spontaneously hypertensive rats (SHR) were treated with enalapril (25-30 mg/kg per day): Group I received treatment from 4 to 14 weeks of age to inhibit development of hypertension and Group R received the drug from 14 to 20 weeks of age to reverse established hypertension. 2. Systolic blood pressure, ploidy of aortic smooth muscle cells (flow cytometric DNA analysis) and aortic hypertrophy (medial cross-sectional area) were determined at times both during and after enalapril treatment (up to 30 weeks). 3. Enalapril treatment normalized blood pressure to that of age-matched Wistar-Kyoto rats in both groups. Blood pressure rose again following cessation of treatment. 4. In untreated SHR the incidence of polyploid cells increased concomitantly with increasing pressure throughout the time studied, whereas in Group I the incidence remained low. In Group R, the incidence of polyploidy directly paralleled both the decrease (normalization) and the rise in blood pressure following cessation of treatment. 5. Hence, the incidence of vascular smooth muscle cell polyploidy is not simply a result of growth of the vessel with increasing age of the SHR, but parallels inhibition, reversal, and redevelopment of hypertension.     

Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders.

Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously investigated as a conventional tablet formulation administered twice daily. More recently considerable experience has been gained with an extended release (ER) formulation which has the convenience of once daily administration. Felodipine ER has been well studied in patients with essential hypertension. As monotherapy in mild to moderate essential hypertension, felodipine ER is at least as effective in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics and ACE inhibitors, with some results favouring felodipine ER at a statistically significant level at the dosages used. It is also effective combined with controlled release metoprolol or enalapril in patients with mild to moderate essential hypertension. In patients with more severe forms of essential hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER was effective as an 'add-on' therapy in placebo-controlled trials, and, at the dosages used, more effective than either sustained release nifedipine or nitrendipine. Felodipine produces effective control of blood pressure without negative effects on cardiac performance. In addition to its antihypertensive action, results suggest that felodipine therapy is associated with significant regression of left ventricular hypertrophy. Furthermore, it appears suitable for use in patients with concomitant diabetes, renal dysfunction or asthma, and is also being investigated for use in patients with congestive heart failure or angina pectoris. Felodipine ER is an effective drug for the treatment of all grades of essential hypertension, and can be used both as monotherapy and in combination with other antihypertensive agents. Further clinical experience should fully establish the long term tolerability of felodipine ER and consequently its place in therapy relative to other accepted antihypertensive drugs. However, with the convenience of once daily administration, felodipine ER is a worthwhile innovation in the treatment of hypertension.     

ORTHOSTATIC HYPOTENSION AFTER THE FIRST ADMINISTRATION OF PRAZOSIN IN HYPERTENSIVE PATIENTS: ROLE OF THE PLASMA VOLUME

1. Prazosin (2 mg, p.o.) was administered to nine patients with essential hypertension while intra-arterial pressure was recorded by an Oxford portable apparatus. In all patients, 30 min-3 h after the administration, systolic and diastolic pressure fell on assuming the upright posture and four patients fainted. No correlation was found between the degree of fall in pressure and the plasma concentration of the drug. Acute expansion of the plasma volume by means of 6% Dextran infusion reduced the orthostatic blood pressure fall in all cases and a significant inverse correlation was found between plasma volume and orthostatic fall of pressure. 2. After ten days of continuous treatment with prazosin, 2 mg daily, a significant decrease in blood pressure was observed while orthostatic hypotension disappeared, probably due to the plasma volume expansion induced by the drug.     

THE EFFECT OF PRAZOSIN THERAPY ON PLATELET ACTIVATION IN ESSENTIAL HYPERTENSION

1. Plasma levels of beta-thromboglobulin, initial and total platelet aggregation (induced by adrenaline or adenosine diphosphate [ADP]) were determined in 26 normotensive subjects and 26 patients with untreated essential hypertension. Groups of 18 essential hypertensive patients and 18 age- and sex-matched normotensives were compared. 2. After 7 days of treatment with prazosin in a dose of 2-8 mg daily the above measures were repeated in 18 essential hypertensive patients. A significant increase in plasma levels of beta-thromboglobulin, initial and total adrenaline-induced as well as ADP-induced platelet aggregation was found in hypertensives. Prazosin restored the mean arterial blood pressure in hypertensives to normal, but it had no significant influence either on increased beta-thromboglobulin levels or on initial and total aggregability. 3. The results confirm increased platelet aggregation and in vivo platelet activation in patients with essential hypertension; however there is a discrepancy with previous reports about those results obtained after prazosin therapy. The results suggest that increased platelet aggregation and in vivo activation need not be restored to normal after effective antihypertensive therapy alone. They give reason for the combination of antihypertensive together with anti-aggregatory therapy in essential hypertension.     

The effect of triple drug therapy on renal function in patients with essential hypertension

The effects of long-term triple drug therapy on renal function in patients with moderate to severe essential hypertension have not been evaluated systematically. We prospectively studied fifteen male patients with moderate to severe essential hypertension receiving triple drug therapy (metolazone, atenolol or betaxolol, and minoxidil) for 16 weeks. Supplemental potassium was prescribed in an attempt to maintain serum potassium above 3.5 mEq/liter. Systemic blood pressure was well controlled with this regimen. However, glomerular filtration rate (assessed by inulin clearance), effective renal plasma flow (assessed by paraaminohippurate clearance), and renal blood flow were reduced. Filtration fraction and renal vascular resistance were not significantly altered. Plasma renin activity remained stimulated throughout the protocol. Weight gain occurred, and serum potassium remained low. These results suggest that triple drug therapy employing a diuretic, beta-adrenergic antagonist, and a potent vasodilator is effective therapy for controlling moderate to severe systemic hypertension. However this antihypertensive regimen may be associated with a decrement in renal function.     

LEFT VENTRICULAR MASS AND MICROALBUMINURIA: RELATION TO AMBULATORY BLOOD PRESSURE

1. Both microalbuminuria and left ventricular hypertrophy may reflect target organ damage in essential hypertension. Both are related to the prevailing level of blood pressure and both are associated with an increase in morbidity and mortality. 2. The database of the Hypertension Diagnostic Service, a multicentre secondary referral clinic for patients with essential hypertension, was analysed in order to clarify the level of association between microalbuminuria and left ventricular hypertrophy, which might explain the observed increase in morbidity and mortality in patients with microalbuminuria. Microalbuminuria was measured semiquantitatively by urine dip-stix. After the exclusion of patients with potential secondary hypertension, renal disease and diabetes mellitus, patients with complete data for microalbuminuria, left ventricular mass (LVM) and 24 h blood pressure monitoring were selected. 3. Data were complete for 704 patients (47% male, age 51 +/- 12 years) and 42% tested positive for microalbuminuria. Microalbuminuria was positively related to 24 h systolic blood pressure and weight and was negatively related to age. Left ventricular mass was higher in patients with microalbuminuria (men, 265 +/- 69 g; women, 207 +/- 61 g) than in those without (men, 250 +/- 64 g, P < 0.05; women, 185 +/- 50 g, P < 0.001). After correction for the effects of gender, body mass index and 24 h systolic blood pressure, the presence of microalbuminuria was associated with an increase in LVM of 10 g (P < 0.05, 95% confidence interval, 2-19 g).     

缬沙坦治疗高血压对左心室肥厚和舒张功能的影响

目的观察缬沙坦的降压疗效及对原发性高血压患者左心室肥厚和舒张功能的影响。方法对46例1—2级原发性高压患者给予口服缬沙坦80-160mg,治疗24周,观察治疗前后血压变化,并用超声心动图观察治疗前后左室结构和舒张功能变化。结果原发性高血压患者应用缬沙坦治疗后,收缩压和舒张压均较治疗前减低（P〈0．05）,左室质量指数（LVMI）较治疗前显著降低（P〈0．01）,心室舒张功能明显改善（P〈0．01）,不良反应轻微。结论缬沙坦有较好的降压疗效,并可逆转左心室肥厚及改善左主室舒张功能。     

伊贝沙坦治疗高血压及对左心室肥厚和舒张功能的影响

目的观察伊贝沙坦的降压疗效及对原发性高血压患者左心室肥厚和舒张功能的影响。方法对54例1-2级原发性高血压患者给予口服伊贝沙坦150～300mg，治疗24周，观察治疗前后血压变化，并用超声心动图观察治疗前后左室结构和舒张功能变化。结果原发性高血压患者应用伊贝沙坦治疗后，收缩压和舒张压均较治疗前减低（p〈0.05），左室质量指数（LVMI）较治疗前显著降低（P〈0．01），心室舒张功能明显改善（P〈0．01），不良反应轻微。结论伊贝沙坦有较好的降压疗效。并可逆转左心室肥厚及改善左心室舒张功能。     

Effects of drug therapy on hypertensive left ventricular hypertrophy

To determine the rate and extent of reversal of left ventricular (LV) hypertrophy, eight patients with moderate to severe essential hypertension (diastolic blood pressure 116 mmHg, s.d. = 8) underwent serial echocardiography during 12 months of closely supervised antihypertensive therapy with multiple drugs. LV cavity size and average wall thickness were measured by sector-directed M-mode echocardiography. LV mass was estimated from a formula which had previously been validated. All subjects had increased LV mass (greater than 125 g/m2). From 6-12 months, 84% of standing diastolic blood pressures, measured monthly, were 90 mmHg or less. During therapy LV mass decreased from 206 g/m2 (s.d. = 98) initially to 168 g/m2 (s.d. = 82) after 6 months (P less than 0.001) with no further significant change by 12 months. In four patients with less severe hypertrophy, LV mass was within the normal range after 6 months of therapy. In four patients with more severe hypertrophy, LV mass remained significantly elevated at 6 and 12 months. Severe hypertensive LV hypertrophy may be only partially reversible, despite good blood pressure control.     

老年高血压患者左室质量与动脉僵硬度关系探讨

摘要目的：探讨老年高血压患者左室肥厚与动脉僵硬度的关系。方法：左室质量指数（LVMI）和脉搏波传导速度（PWV）分别作为评价左室肥厚和动脉僵硬度的指标，对108例老年高血压病患者的LYMI与PWV及其他影响因素之间进行简单相关分析及逐步回归分析。并对不同程度左室肥厚的PWV值进行比较。结果：LYMI与PWV、收缩压、舒张压、脉压、高血压病程、性别及体质量指数呈正相关，与高血压的治疗呈负相关。PWV、高血压治疗、性别和舒张压进入最优回归方程。PWV在左室肥厚者明显高于无左室肥厚者，左室肥厚越明显则PWV越高（F=24．473，P〈0.001）：结论：动脉僵硬度增加是导致老年高血压患者左室肥厚的重要原因。     

RENIN AND ANGIOTENSIN-CONVERTING ENZYME GENOTYPES IN PATIENTS WITH ESSENTIAL HYPERTENSION AND LEFT VENTRICULAR HYPERTROPHY

1. The associations between left ventricular hypertrophy (LVH) and specific alleles of the renin and angiotensin-converting enzyme (ACE) genes were studied in patients with essential hypertension and normal blood pressure. 2. LVH was present in 42% of those with essential hypertension (n= 72) and 17% of those with normal blood pressure (n= 44). 3. The frequency of each renin allele was the same in hypertensive and in normotensive patients. Renin allele frequencies were also the same for those with LVH and those with normal cardiac mass. When only hypertensives were considered, renin alleles were in the same proportion for the groups with and without LVH. Similarly, ACE alleles were not associated with essential hypertension nor with elevated cardiac mass. 4. We conclude that, in this population, variations in the renin or ACE genes do not contribute significantly to the development of LVH or to essential hypertension.     

THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.     

Valsartan: a novel angiotensin Type 1 receptor antagonist

Valsartan is a highly selective, orally available antagonist of the angiotensin Type 1 (AT₁)receptor. It is indicated for treatment of mild to moderate essential hypertension. Experimental studies have confirmed the abolition or attenuation of angiotensin II (AII)-related effects, such as vasoconstriction, cell growth promotion and aldosterone release. In humans, valsartan is rapidly absorbed with maximal plasma concentrations occurring 1 - 2 h after oral administration. The elimination half-life comes to about 7 - 8 h, valsartan is metabolised to a negligible extent and most of the drug is excreted via the faeces. There is no dose adjustment required for patients with a creatinine clearance >> 10 ml/min. The dose should not exceed 80 mg o.d. in patients with hepatic dysfunction, valsartan is not recommended for patients with severe hepatic dysfunction and/or biliary cirrhosis. At present, no clinically relevant pharmacokinetic drug interactions have been observed. Valsartan produces persistent blood pressure reductions in patients with mild to moderate hypertension, the recommended starting dose is 80 mg o.d. If required, the dose may either be increased to 160 mg o.d. or hydrochlorothiazide may be added. In comparison to other antihypertensive drugs valsartan therapy leads to similar blood pressure reductions, while exhibiting a favourable tolerability profile. Preliminary studies suggest beneficial effects in patients with hypertensive end-organ damage such as renal disease and left ventricular hypertrophy. Furthermore, the drug is evaluated for its efficacy in heart failure and patients post-myocardial infarction.