Converting Enzyme Inhibition in Mild and Moderate Essential Hypertension. II

ABSTRACT. In 24 patients with mild/moderate essential hypertension, we studied the effects of captopril with/without hydrochlorothiazide (Htz) on blood pressure, the renin-angiotensin system, blood bradykinin concentration (BBK), plasma volume, exchangeable sodium and glomerular filtration. Daily captopril doses of 75 and 150 mg were equally effective in reducing the blood pressure. Addition of Htz caused further blood pressure reductions. Nineteen patients attained a diastolic blood pressure ≤90 mmHg. Angiotensin converting enzyme inhibition with captopril led to a fall in plasma concentrations of angiotensin II (PAII) and renin substrate, and an increase in plasma concentrations of renin and angiotensin I. Patients starting with Htz had a higher PAII and subsequently a larger fall in blood pressure on captopril than untreated patients. BBK remained unchanged, indicating that the hypotensive action of captopril does not involve an accumulation of circulating kinin. Body fluid volumes and renal function were not affected by the various treatment regimens.     

The Effects of Twice Daily Captopril and Once Daily Enalapril on Ambulatory Intraarterial Blood Pressure in Essential Hypertension

Intraarterial ambulatory pressure (AP) was recorded before and during therapy with captopril or enalapril in two groups with hypertension. Seven patients were admitted during the study. The. monitoring of AP and heart rate (HR) was performed during placebo therapy and following a minimum period of 7 days of 25 mg twice daily captopril or 2.5 to 10 mg once daily enalapril. The AP and HR following percutaneous insertion of a cannula into the brachial artery were sampled then data were analyzed as reported previously.

After the cannula was inserted, examinations of tilt-up, handgrip and ergometer were performed. Both drugs produced a significant reduction of ambulatory AP throughout 24 hours with preservation of the overall shape of the circadian curve. The results also demonstrated that both drugs had not affected normal daily activities. Thus, twice daily captopril and once daily enalapril can be used as the first-line therapy of hypertension.     

Angiotensin Converting Enzyme Inhibition Reveals an Important Role for the Renin System in the Control of Normal and High Blood Pressure in Man

Captopril, given for 5 days to normotensive healthy subjects caused a significant fall in blood pressure. The fall in mean supine blood pressure was greater on a low sodium diet (10 mmols/ day) - 19.6% and was less on a high sodium diet (350 mmols/day) - 11% compared to the normal sodium intake (120 mmols/day) when the fall in blood pressure was 16.5%. Patients with essential hypertension who were studied on their normal diet had a similar fall in blood pressure for a given plasma renin activity. It seems likely that the predominant mechanism whereby captopril lowers blood pressure is through the inhibition of the formation of angiotensin II. If this is so, our results suggest that the renin system is an important control of both normal and high blood pressure when on a normal sodium intake.     

Relationship between Insulin Resistance and the Renin-Angiotensin System: Analysis for Patients with Essential and Renovascular Hypertension

Insulin resistance is frequently observed in patients with essential hypertension (EHT), and the renin-angiotensin system (RAS) has been demonstrated to modulate the status of insulin resistance. The aims of present study are to investigate the relationship between systemic RAS and insulin resistance in 82 patients with EHT and compare the impact of RAS to insulin resistance with 10 renovascular hypertension (RVHT) patients who have a highly activated systemic RAS. From patients who were admitted to our hospital, patients with overt diabetes and hypertensives who had secondary HT except RVHT or chronic renal failure were excluded. Plasma renin activity (PRA) was used as an indicator of systemic RAS activity. HOMA-R as an index of insulin resistance and sum of immunoreactive insulin (IRI) during glucose tolerance test (∑IRI) and IRI at 120 minutes (IRI120) were used as indices of hyperinsulinemia. In the EHT patients, circulating PRA showed an independent relationship with IRI120 and ∑IRI after adjusting confounding factors (IRI120: t?=?2.70, p?=?0.01, ∑IRI: t?=?3.05, p < 0.001). Excluding patients who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blocker (ARBs), the relationship remained in univariate linear regression; after adjustment for confounding factors, PRA showed a tendency to be correlated with ∑IRI. However, there was no significant relationship between PRA and indices of insulin resistance and hyperinsulinemia in patients with RVHT. In conclusion, the systemic RAS may modulate insulin sensitivity in EHT patients.     

Effect of Ketoprofen on Blood Pressure, Endocrine and Renal Responses to Chronic Dosing with Captopril in Patients with Essential Hypertension

The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered. Twelve patients with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or matching placebo in a randomized double-blind cross-over fashion. A 3-week wash-out period was included between treatment periods. Blood pressure on the first and last days of the placebo treatment period (137± 7(SD)/80±8 and 139±11/81±9 mmHg) was similar to respective values during ketoprofen therapy (136±10/79±7 and 143 ± 10/81 ± 9 mmHg). The mean differences in systolic and diastolic blood pressures, at the end of the treatment periods, between ketoprofen and placebo were 4(95% confidence intervals -5, +13) and 0(-8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium excretion (160 ± 33 and 147 ± 39 mmol/24 h for ketoprofen and placebo, respectively). Ketoprofen was without effect on glomerular filtration rate, renal plasma flow and filtration fraction. In conclusion, our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril.     

Acute and Chronic Effects of a Hypocaloric Diet on 24-Hour Blood Pressure,Heart Rate and Heart-Rate Variability in Mildly-to-Moderately Obese Patients with Essential Hypertension

We examined the acute and chronic effects of a nutritionally balanced, moderately hypocaloric diet on 24-hour ambulatory blood pressure, heart rate and heart-rate variability in mildly-to-moderately obese patients with essential hypertension. We enrolled 16 obese patients with essential hypertension [age: 51–76 years, body mass index (BMI): 26–32 kg/m²]. For the initial week, a standard diet of 2,000 kcal/day was given, followed by a 3-week of a hypocaloric diet of 850 kcal/day. In the last period of the standard diet and in the first and the last periods of the hypocaloric diet, each subject's 24-hour ambulatory blood pressure, heart rate and R-R intervals of the electrocardiogram were recorded, and electrolytes and catecholamines in 24-hour urine samples were also measured. A power spectral analysis of the heart-rate variability was performed over a 24-hour period based on the autoregressive method. The subjects lost 3.7 ± 0.3 kg (mean ± s. e. m.) of body     

福辛普利对原发性高血压患者降压作用和对内皮功能的影响

目的评价福辛普利对轻、中度原发性高血压患者的降压疗效,以及对原发性高血压患者内皮功能和肾素-血管紧张素系统(RAS)影响的机制.方法60例原发性高血压患者,随机分为福辛普利组30例和吲哒帕胺组30例.观察治疗前与治疗后6周,诊所血压(CBP)、血浆一氧化氮、内皮素、肾素活性、血管紧张素Ⅱ和醛固酮浓度变化,并对CBP和RAS、血压水平与内皮功能之间的相关性进行分析.结果治疗后2组血压水平显著下降,福辛普利组收缩压从160士14mmHg降至149±13mmHg,舒张压从96±7mmHg降至84±6mmHg,吲哒帕胺组收缩压从161±16mmHg降至154±14mmHg,舒张压从94±6mmHg降至85±7mmHg,差异有极显著性(P均＜0.001).福辛普利组血浆一氧化氮升高,肾素活性上升,内皮素下降,血管紧张素Ⅱ下降,醛固酮下降,差异有极显著性(P均＜0.001),吲哒帕胺组上述参数未见明显变化(P均＞0.05).结论福辛普利对于轻、中度原发性高血压患者疗效显著,福辛普利降压同时能改善动脉内皮功能,降低RAS活性.     

Randomised,Double-Blind Crossover Comparison of Once-Daily Captopril and Lisinopril in Patients with Mild to Moderate Hypertension - a Community-Based Study: By Hunter Hypertension Research Group,Discipline of Clinical Pharmacology,Newcastle Mater Misericordiae Hospital,Waratah 2298 NSW Australia

Of twenty-five patients with mild to moderate hypertension, recruited and managed in the community, seventeen responded fully to, and completed a randomised cross-over study of, captopril (ceiling dose 100 mg) compared with lisinopril (ceiling dose 40 mg) both given as a single daily dose. Mean supine and standing blood pressures measured at the end of the dose interval were significantly reduced compared to placebo by both compounds at three and six weeks. However, a consistent, significant increase in blood pressure occurred between three and six weeks in both arms of the study despite good and unchanged compliance with a fixed dose of each medication. Both captopril and lisinopril were well tolerated. Drug-related cough was the principal adverse effect.     

Effects of a Fixed Combination of Low Dose Nifedipine and Acebutolol on Essential Hypertension: Comparison with Standard Dose Acebutolol

114 patients from four clinics participated in a double blind study designed to assess the efficacy of a nifedipine-acebutolol fixed combination ?10 mg + 100 mg as compared with acebutolol ?200 mg- in essential hypertension. During the ten week study the mean blood pressure readings (s.d.) 1–3 h after treatment decreased from 179.2/104.8 (10.2/6.2) to 150.3/87.7 (9.8/7.7) in the combination group and from 181.71106.5 (14.4/7.0) to 150.4189.0 (15.0/10.4) in the acebutolol group. The mean systolic and diastolic blood pressures were also decreased after exertion (load) and 24 hours after treatment at the end of the 6th week of the study. A doubling of the dose from week 7 to 10 did not change these figures. These results reveal the possibility of treating essential hypertension with a low dose of beta-adrenergic blocking agents in combination with 10 mg nif edipine. Both drugs were well tolerated. 3 patients (5 %) in the combination group and 3 patients in the acebutolol group were withdrawn from the study because of headache and dizziness.     

Effects of a Dual L/N-Type Calcium Channel Blocker Cilnidipine on Blood Pressure,Pulse Rate,and Autonomic Functions in Patients with Mild to Moderate Hypertension

The current study was conducted to examine the effects of cilnidipine, a dual L/N-type calcium channel blocker, on blood pressure, pulse rate, and autonomic functions in patients with mild-to-moderate hypertension. Sixteen patients with mild-to-moderate hypertension (8 males and 8 females; 44–72 years of age) were treated with cilnidipine (10 mg/day) for 3 months. Before and after the treatment, the following measurements were conducted; beat-to-beat blood pressure during late phase II and overshoot phase of the Valsalva maneuver, the Valsalva ratio, heart rate response to deep breathing, systolic and diastolic blood pressure, and pulse rate. The head-up tilt test was also performed before and after the treatment. Cilnidipine significantly decreased either the systolic or diastolic blood pressure from 151 ± 15 mmHg to 129 ± 14 mmHg or 84 ± 11 mmHg to 71 ± 9 mmHg, respectively. For pulse rate, there were no significant changes during therapy. Beat-to-beat blood pressure during late phase II and overshoot phase of the Valsalva maneuver indicated significant improvements in both figures. The heart rate response to deep breathing and the Valsalva ratio indicated no significant differences during therapy. Before and after the treatment, no orthostatic hypotension was observed during the head-up tilt test. The current study revealed that cilnidipine significantly decreases blood pressure with improving autonomic functions while having no adverse effects on heart rate response and pulse rate.     

氯沙坦、福辛普利及硝苯地平控释剂对原发性高血压患者诊所血压及24小时动态血压作用之比较

目的探讨氯沙坦、福辛普利和硝苯地平控释剂对原发性高血压患者诊所血压及昼夜血压的影响,并进行比较.方法87例轻、中度原发性高血压患者随机分为3组,分别服用氯沙坦50?mg/d(L组,30例)、福辛普利10?mg/d(F组,28例)和硝苯地平控释剂30?mg/d(N组,29例),比较治疗前及治疗4周末对诊所血压(OBP)[BFQ、动态血压的影响.结果3组治疗4周末OBP、动态血压均较服药前降低,有显著性差异([WTBXP＜0.05～0.001),3组间无显著性差异;各组均能维持正常的血压昼夜节律,24小时血压谷/峰(T/P)均大于70%;以N组作用显著.各组不良反应发生率分别为F组39.4%、N组43.8%、L组18.2%,N组24小时平均心率较治疗前明显加快(P＜0.05).结论氯沙坦、福辛普利和硝苯地平控释剂均能有效持续降低血压.治疗后硝苯地平控释剂24小时血压谷/峰优于氯沙坦和福辛普利.氯沙坦服药后的耐受性优于福辛普利及硝苯地平控释剂.     

Long-Term Enalapril-A New Converting Enzyme Inhibitor-in the Treatment of Mild to Moderate Essential Hypertension,Results of a worldwide Multiclinic Study. Subtitle: Comparing Two Ways of Analyzing Data

The antihypertensive effect of enalapril maleate, a new converting enzyme inhibitor, was evaluated in a multiclinic, double-blind, randomized study in patients with mild to moderate essential hypertension. The analyses were done in two ways, with patients who violated the entry criteria of the protocol excluded, and according to the intention to treat principle. Enalapril in dosages of 10 to 40 mg daily administered alone or concomitantly with hydrochlorothiazide was compared to propranolol (80 to 240 mg daily) alone or concomitantly with the diuretic. The study showed that enalapril significantly lowered both systolic and diastolic blood pressure. At each timepoint measured in the course of 26 weeks of therapy, the patients in the enalapril group consistently had greater decreases in blood pressure than patients in the propranolol group although not always significantly. The enalapril treatment group had a decrease in the mean arterial blood pressure of 22.2 mmHg compared to the propranolol group of 17.9 m H g at the end of the study. These results were similarly independent of the way the data were analyzed. Fewer patients in the enalapril group required the addition of hydrochlorothiazide to maintain optimal control of blood pressure. Enalapril was found to be safe and well tolerated over the long-term of 48 weeks. effects such as leukopenia and taste perversions believed to be sulfhydrylrelated were not encountered. rare. Thi azide induced hypokal emia, hyperuricemia and hyperglycemia appeared to be attenuated by enalapril. The favorable efficacy and side-effect profile provide the basis for enalapril to be a drug of choice when initiating antihypertensive therapy. Side The occurrence of rash and proteinuria was     

Felodipine or Hydrochlorothiazide/Triamterene for Treatment of Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters

Trenkwalder P, Plaschke M, Aulehner R, Lydtin H. Felodipine or Hydrochlorothiazide/Triamterene for Treatment of' Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters.

The aim of the study was to compare the antihypertensive efficacy of either felodipine or the diuretic combination hydrochlorothiazide/triamterene in a group (n = 65) of elderly (≥70 years) hypertensives (office blood pressure ≥ 60/95 mmHg) with special regard to ambulatory blood pressure monitoring, hypertensive heart disease and metabolic parameters. This was a randomized, double-blind study with a treatment period of 6 months. Reduction of office and 24-hr ambulatory blood pressure was comparable with both treatment regimens; after 6 months, 18 of 29 patients in the felodipine group (62%) and 20 of 27 patients in the diuretic group (74%; p = 0.4) were controlled. While episodes of ischemic type ST-segment depression were significantly reduced in the felodipine group (from 49 to 9 episodes), there was no significant change in the diuretic group (from 24 to 21 episodes). Both regimens decreased left ventricular wall thickness, but the decline in left ventricular muscle mass index was significant only for felodipine. Felodipine did not induce any change in metabolic or hormonal parameters; the diuretic combination significantly increased serum creatinine, uric acid, plasma renin activity, and plasma prorenin. Thus, the antihypertensive efficacy of felodipine and the diuretic combination was comparable in elderly hypertensives; only felodipine, however, improved parameters of hypertensive heart diesease and showed a neutral metabolic and hormonal profile.     

阿利沙坦酯与贝尼地平对轻中度高血压患者降压效果、肾功能及血尿酸影响的对比研究

背景近年研究发现,钙通道阻滞剂(CCB)贝尼地平具有降低尿蛋白的作用。血管紧张素Ⅱ受体拮抗剂(ARB)阿利沙坦酯是我国首个自主研发的1.1类抗高血压药。但目前有关贝尼地平与阿利沙坦酯治疗高血压的研究报道少见。目的比较阿利沙坦酯和贝尼地平对轻中度高血压患者降压效果、肾功能及血尿酸的影响。方法选取2020年1月至2021年6月深圳大学总医院心血管内科、肾内科门诊及住院部收治的新发高血压患者92例,采用随机数字表法分为阿利沙坦酯组(n=45)和贝尼地平组(n=47)。贝尼地平组患者给予贝尼地平治疗,阿利沙坦酯组患者给予阿利沙坦酯治疗。比较两组患者治疗前及治疗12周后24 h平均血压(包括24 h平均收缩压和24 h平均舒张压)、肾功能指标(包括血肌酐、血β₂-微量蛋白、尿微量白蛋白/尿肌酐比值、尿总蛋白/尿肌酐比值)及血尿酸,并观察两组患者治疗期间不良反应发生情况。结果两组患者治疗前及治疗12周后24 h平均收缩压、24 h平均舒张压比较,差异无统计学意义(P>0.05);治疗12周后,两组患者24 h平均收缩压和24 h平均舒张压分别低于本组治疗前(P<0.05)。两组患者治疗前及治疗12周后血肌酐、血β₂-微量蛋白、尿微量白蛋白/尿肌酐比值、尿总蛋白/尿肌酐比值、血尿酸比较,差异无统计学意义(P>0.05);治疗12周后,两组患者血肌酐、血β₂-微量蛋白、尿微量白蛋白/尿肌酐比值、尿总蛋白/尿肌酐比值、血尿酸分别低于本组治疗前(P<0.05)。两组患者治疗期间均未出现明显不良反应。结论阿利沙坦酯与贝尼地平对轻中度高血压患者的降压效果及肾功能的改善效果相似,但对于轻中度高血压合并高尿酸血症患者推荐使用阿利沙坦酯。