Cardiovascular effects of combination of perindopril, candesartan, and amlodipine in hypertensive rats

The combination therapy with ACE inhibitors, angiotensin II type 1 (AT(1)) receptor antagonists, or calcium channel antagonists may exert more beneficial effects on cardiovascular diseases than monotherapy. Perindopril, candesartan cilexetil, or amlodipine alone or the combination of low doses of each agent was administered orally to stroke-prone spontaneously hypertensive rats (SHRSP) for 4 weeks to compare the hypotensive or cardiovascular effects. Although perindopril (2 mg/kg), candesartan cilexetil (2 mg/kg), or amlodipine (3 mg/kg) alone caused comparable hypotensive effects in SHRSP, monotherapy with perindopril or candesartan decreased left ventricular (LV) weight; mRNA levels for atrial natriuretic factor, skeletal alpha-actin, and collagen types I and III; and aortic weight and platelet-derived growth factor-beta receptor tyrosine phosphorylation to a greater extent than monotherapy with amlodipine. Although monotherapy with a low dose (0.2 mg/kg) of perindopril or candesartan cilexetil did not significantly reduce the LV mRNA levels and aortic platelet-derived growth factor-beta receptor phosphorylation of the SHRSP, combination therapy at such a low dose normalized these parameters more potently than the use of amlodipine (3 mg/kg) alone. Although perindopril or candesartan cilexetil alone at 0.05 mg/kg did not decrease the blood pressure of the SHRSP, such a low dose of combination therapy decreased LV weight and atrial natriuretic factor mRNA levels of the SHRSP to a greater extent than amlodipine alone or amlodipine combined with perindopril or candesartan cilexetil. Our results provide evidence that suggests the combination of an ACE inhibitor and an AT(1) receptor antagonist may be more effective in the treatment of cardiac and vascular diseases than the combination of a calcium channel blocker with an ACE inhibitor or an AT(1) receptor antagonist or monotherapy with each agent.     

Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.     

Indapamide SR versus candesartan and amlodipine in hypertension: the X-CELLENT Study

BACKGROUND: Reducing systolic blood pressure (BP) is of major benefit to patients with isolated systolic hypertension, but lowering normal diastolic BP may be harmful in terms of cardiovascular risk. Effects of different drugs on systolic BP, diastolic BP, and pulse pressure are therefore of interest. METHODS: The NatriliX SR versus CandEsartan and amLodipine in the reduction of systoLic blood prEssure in hyperteNsive patienTs study (X-CELLENT) was a randomized, double-blind, placebo-controlled study comparing the effects of three drugs on these BP components. Patients with systolic-diastolic or isolated systolic hypertension (n = 1758) received indapamide (1.5 mg) sustained release (SR), candesartan (8 mg), amlodipine (5 mg), or placebo once daily for 12 weeks. RESULTS: Compared to placebo all active treatments reduced all BP components significantly (P < .001). For the patients with isolated systolic hypertension (n = 388), the three treatments significantly reduced systolic BP, but only indapamide SR did not change diastolic BP and thus reduced pulse pressure significantly relative to placebo (P = .005). In an ancillary study using ambulatory BP monitoring (n = 576), all three treatments significantly reduced BP components during 24 h relative to placebo. Changes in systolic BP and pulse pressure were similar with the three treatments, but the reduction in diastolic BP was significantly smaller, and therefore more favorable, with indapamide SR compared with candesartan (P = .039). In patients with isolated systolic hypertension (n = 106), indapamide SR reduced 24-h systolic BP significantly more than amlodipine (P = .037), and only indapamide SR reduced 24-h pulse pressure significantly relative to placebo (P = .03). All three drugs were well tolerated. CONCLUSIONS: This distinctive BP-lowering profile of indapamide SR seems highly beneficial when compared to the either of candesartan or amlodipine.     

Effects of up-titration of candesartan versus candesartan plus amlodipine on kidney function in type 2 diabetic patients with albuminuria

In the present study, we tested the hypothesis that up-titrating the dose of an angiotensin receptor blocker (ARB) is superior to combined treatment with an ARB and a calcium channel blocker for the same degree of blood pressure (BP) reduction, with respect to urinary albumin excretion in diabetic patients treated with a standard dose of the ARB. Hypertensive patients with type 2 diabetes mellitus and albuminuria (≥30?mg?g(-1) creatinine) were enroled in the study, and were either started on or switched to candesartan (8?mg per day) monotherapy. After a 12-week run-in period, baseline evaluations were performed and patients with BP ≥130/80?mm?Hg were randomly assigned to receive either candesartan (12?mg per day) or candesartan (8?mg per day) plus amlodipine (2.5?mg per day) for a further 12 weeks. The primary end-point was a reduction in urinary albumin levels. Although there was no significant difference in the BP reduction between the two groups, the reduction in urinary albumin was greater in the up-titrated than the combination therapy group (-40±14% vs -9±38%, respectively; P<0.0001). Thus, up-titration of candesartan more effectively reduces urinary albumin excretion than combined candesartan plus amlodipine in hypertensive patients with diabetes for the same degree of BP reduction.     

Effects of candesartan compared with amlodipine in hypertensive patients with high cardiovascular risks: candesartan antihypertensive survival evaluation in Japan trial

The Candesartan Antihypertensive Survival Evaluation in Japan Trial was designed to compare the long-term effects of the angiotensin II receptor blocker candesartan and the calcium channel blocker amlodipine on the incidence of cardiovascular events, represented as a composite of sudden death and cerebrovascular, cardiac, renal, and vascular events in high-risk Japanese hypertensive patients. We conducted a prospective, randomized, open-label study with blinded assessment of the end point in 4728 Japanese hypertensive patients (mean age: 63.8 years; mean body mass index: 24.6 kg/m(2)). Patients were followed for an average of 3.2 years. Blood pressure was well controlled with both treatment-based regimens (systolic blood pressure/diastolic blood pressure: 136.1/77.3 mm Hg for candesartan-based regimens and 134.4/76.7 mm Hg for amlodipine-based regimens after 3 years). Primary cardiovascular events occurred in 134 patients with both the candesartan- and amlodipine-based regimens. The 2 treatment-based regimens produced no significant differences in cardiovascular morbidity or mortality in the high-risk Japanese hypertensive patients (hazard ratio: 1.01; 95% CI: 0.79 to 1.28; P=0.969). In each primary end point category, there was no significant difference between the 2 treatment-based regimens. New-onset diabetes occurred in fewer patients taking candesartan (8.7/1000 person-years) than in those taking amlodipine (13.6/1000 person-years), which resulted in a 36% relative risk reduction (hazard ratio: 0.64; 95% CI: 0.43 to 0.97; P=0.033). We disclosed that candesartan-based and amlodipine-based regimens produced no statistical differences in terms of the primary cardiovascular end point, whereas candesartan prevented new-onset diabetes more effectively than amlodipine.     

Comparative study of the effects of chondroitin sulfate isomers on atherosclerotic subjects.

Effects of isomers of chondroitin sulfate on atherosclerosis were clinically compared, based on sulfate linkage and the amount of sulfate, by using chondroitin 4-sulfate, chondroitin 6-sulfate and chondroitin polysulfate. Fourty eight age-matched atherosclerotic subjects were selected from a home for the elderly in order to the treatment with the agents. The isomers of chondroitin sulfate were given a daily dose of 4.5 g perorally. During the experimental period for 64 months, mortality, serum cholesterol, thrombus-formation time and thrombus weight were examined. The result obtained was as follows: mortality in the groups treated with the isomers of chondroitin sulfate was less than the age-matched untreated control group. Serum cholesterol value in the group treated by the isomers of chondroitin sulfate, chondroitin polysulfate group in particular, fell lower than the pre-treatment value. Thrombus formation time prolonged 150% in the group treated with chondroitin polysulfate over the untreated control group and the resultant thrombus weight was reduced in the treated group. Thus, these data indicated that the isomers of chondroitin sulfate are clinically effective on the treatment of atherosclerosis in the order of chondroitin polysulfate, chondroitin 4-sulfate and/or chondroitin 6-sulfate.     

Efficacy of candesartan cilexetil alone or in combination with amlodipine and hydrochlorothiazide in moderate-to-severe hypertension. UK and Israel Candesartan Investigators

This multicenter study evaluated the efficacy of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension. After a 2-week, single-blind, placebo run-in period, patients entered a 12-week, open-label, dose-titration period. The candesartan cilexetil dose was increased from 8 to 16 mg once daily; amlodipine (5 mg once daily), hydrochlorothiazide (25 mg once daily), and additional medication were also added sequentially if necessary. Patients then entered a final 4-week, parallel-group, double-blind, randomized, placebo-controlled withdrawal period of candesartan alone. A total of 216 patients were recruited. After a 2-week run-in period on placebo tablets, mean sitting blood pressure (BP) was 175/108 mm Hg. At the end of the 12-week dose-titration/maintenance period, mean sitting BP fell to 141/88 mm Hg. In 67 patients who were randomized to placebo and had their candesartan withdrawn, there was a highly significant increase in mean systolic/diastolic BP (13/6 mm Hg) compared with those patients who continued with candesartan (ANCOVA, P:<0.0001). In conclusion, candesartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension. The drug was well tolerated throughout the investigation period.     

Effectiveness of add-on low-dose diuretics in combination therapy for hypertension: losartan/hydrochlorothiazide vs. candesartan/amlodipine.

In guidelines, a combination therapy of two or more antihypertensives is recommended for treatment of hypertension where monotherapy is ineffective. Although diuretics or calcium channel blockers are commonly used as add-ons to angiotensin receptor blocker (ARB), the most effective and safe combination has not been established. In this randomized 4-month study, the efficacy and safety were compared between an ARB/diuretics (losartan/hydrochlorothiazide [HCTZ]) combination and the most prescribed combination, ARB/calcium channel blocker (candesartan/amlodipine) in hypertensive patients for whom 8 mg/day of candesartan proved ineffective. After 36 patients were recruited and allocated into two groups, changes in blood pressure (BP) and laboratory values were analyzed in 31 patients: 16 patients received losartan (50 mg/day)/HCTZ (12.5 mg/day) (L/H group), and 15 patients received candesartan (8 mg/day)/amlodipine (5 mg/day) (C/A group) after 5 patients were withdrawn. After 4 months, L/H significantly (p<0.001) reduced mean systolic BP (SBP)/diastolic BP (DBP) from baseline 160/89 +/- 13/11 mmHg to 140/80 +/- 9/8 mmHg, and C/A reduced BP from 161/90 +/- 10/11 mmHg to 141/79 +/- 10/7 mmHg. The efficacy in reducing BP was similar between the two combination therapies. L/H significantly reduced serum potassium, but within the normal range, and did not increase serum uric acid or serum triglyceride. With L/H, the percentage of patients who attained the BP goal in SBP was higher in elderly patients than in younger patients. As L/H is more cost-effective than candesartan/amlodipine and has fewer adverse effects on uric acid and other metabolic parameters than diuretic monotherapy, it is concluded to be useful for the management of hypertension.     

Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.     

Beneficial action of candesartan cilexetil plus amlodipine or ACE inhibitors in chronic nondiabetic renal disease

Although multiple antihypertensive agents are required to control blood pressure (BP) in chronic renal disease, it remains undetermined whether the combination therapy with angiotensin receptor blockers (ARB) plus calcium antagonists or angiotensin-converting enzyme inhibitors (ACEI) confers more preferable action on renal disease than the ARB monotherapy. In the present study, we compared the effect of the combination therapy with ARB plus calcium antagonists/ACEI on proteinuria with that of the ARB monotherapy in chronic nondiabetic renal disease. At 1 month of the drug treatment, the candesartan monotherapy (n=19) reduced BP from 154+/-3/93+/-2 to 146+/-3/88+/-2 mmHg (P<0.05), and a similar magnitude of BP reductions was observed with the combination therapy with candesartan plus ACEI/amlodipine (from 153+/-2/95+/-2 to 144+/-2/88+/-2 mmHg, P<0.05, n=39). The depressor action of these therapies was sustained throughout the 12-month treatment. In contrast, the reduction in proteinuria was greater with the combination therapy (-52+/-3% at 12 months, n=39) than with the candesartan monotherapy (-25+/-3%, n=19), although the baseline values of proteinuria were nearly the same in the candesartan monotherapy group (1.74+/-0.22 g/day) and the combination therapy group (2.10+/-0.19 g/day, P>0.2). Of note, the proteinuria-sparing effect did not differ between the candesartan+ACEI group and the candesartan+amlodipine group. In conclusion, the present study suggests more beneficial action of the combination therapy with ARB plus ACEI/amlodipine than the ARB monotherapy in nondiabetic renal disease. Since the reduction in BP was achieved to the same level, the distinct proteinuria-sparing action of these therapies is attributed to BP-independent mechanisms, which should vary depending on the agents used.     

坎地沙坦与氨氯地平对高血压左室肥厚患者心功能和尿微量白蛋白的疗效观察

目的探讨坎地沙坦和氨氯地平对高血压患者左室肥厚和尿微量白蛋白的疗效。方法对83例门诊原发性高血压(1级、2级)并左室肥厚患者随机分为坎地沙坦组(42例)和氨氯地平组(41例),分别予以坎地沙坦和氨氯地平治疗。于受试前、后分别测定血压及二维彩色B超,检测室间隔(IVS)、左室后壁厚度(LVPW)、左室舒张末内径(LVDd)、E/A、左室射血分数(EF)和左室重量指数(LVMI),同时测定尿微量白蛋白、血清尿素氮和肌酐。结果两组在受试2周后与治疗前相比,血压均开始明显下降(P<0.01),两组降压疗效相比差异无统计学意义。两组24周测IVS、LVPW、LVDd和LVMI,较治疗前明显降低(P<0.01),EF和E/A升高(P<0.01),24周后坎地沙坦组优于氨氯地平组(P<0.05)。两组治疗4周后尿微量白蛋白都有明显下降(P<0.01)。坎地沙坦组随用药时间的延长,尿微量白蛋白不断降低,24周后明显优于氨氯地平组(P<0.01)。两组治疗前后血清尿素氮和肌酐无明显变化(P>0.05)。结论坎地沙坦和氨氯地平都有良好的降压作用,并且能逆转左室肥厚、降低尿微量白蛋白,但坎地沙坦的保护作用优于氨氯地平。     

Effects of amlodipine and candesartan on oxidized LDL level in patients with mild to moderate essential hypertension

Objective. To compare the effects of amlodipine and candesartan on oxidized low-density lipoprotein (OxLDL), conjugated dienes (CD) and baseline diene conjugation in circulating low-density lipoproteins (LDL-BDC) level during antihypertensive treatment. Methods. Forty-nine patients with untreated mild to moderate essential hypertension were recruited in a randomized double-blind study to receive a daily dose either of 8 mg candesartan or 5 mg amlodipine for 16 weeks. Blood pressure, OxLDL, CD, LDL-BDC, triglycerides (TG), total cholesterol and lipoprotein cholesterol were measured at baseline, at week 2 and at week 16. Results. During treatment, in addition to a significant decrease in systolic and diastolic blood pressure, high level of OxLDL decreased significantly reaching practically upper kit reference values. Both treatment groups were similar with regard to the studied parameters at all time points. At the same time serum TG, lipoprotein and total cholesterol levels as well as LDL-BDC did not change and CD levels did not exceed endemic normal. Decrease in both systolic and diastolic blood pressure was associated with decrease in LDL-BDC/LDL. Conclusions. Besides their antihypertensive effects, both candesartan and amlodipine are efficient drugs for reducing OxLDL level, being neutral with regard to serum lipids.     

Distinct effects of amlodipine treatment on vascular elastocalcinosis and stiffness in a rat model of isolated systolic hypertension

OBJECTIVE: Medial elastocalcinosis (MEC) contributes to the development of large artery stiffness and isolated systolic hypertension. Since endothelin receptor antagonists can prevent and regress elastocalcinosis, our aim was to determine whether amlodipine, a calcium channel blocker that inhibits endothelin signaling, could likewise influence MEC, or reduce pressure mainly through its vasorelaxing properties. METHODS: Control male Wistar rats were compared with rats receiving warfarin (20 mg/kg per day) with vitamin K1 (15 mg/kg per day) alone (WVK) or in association with amlodipine (15 mg/kg per day) for 4 weeks or during the last week or last 4 weeks of an 8-week WVK treatment (two regression groups). RESULTS: Inactivation of matrix Gla protein by WVK for 4 or 8 weeks increased the calcium content 10-fold in the aorta, inducing a significant elevation of pulse wave velocity and pulse pressure by selective augmentation of systolic blood pressure. Amlodipine prevented aortic MEC, pulse wave velocity and pulse pressure elevation, but reversed only MEC and pulse pressure when administered for 4 weeks. One week of amlodipine administered after 7 weeks of WVK partially decreased pulse pressure without modifying aortic MEC. Amlodipine did not reduce the fibrosis associated with calcified areas in the WVK model during the regression protocols. CONCLUSION: The clinical efficacy of amlodipine in improving hemodynamic variables and reducing cardiovascular events in isolated systolic hypertension could be explained by its beneficial effect on vascular calcification. Amlodipine's lack of effect on pulse wave velocity and collagen deposition, however, suggests that it may reduce pulse pressure by means other than improving arterial stiffness.     

Comparative effect of fixed-dose combination tablets of candesartan cilexetil/amlodipine versus olmesartan medoxomil/azelnidipine on laboratory parameters in patients with hypertension: a retrospective cohort study

We conducted a retrospective cohort study to evaluate and compare the long-term effects of two single-pill fixed-dose combinations (FDCs), candesartan/amlodipine and olmesartan/azelnidipine, on laboratory parameters in patients in routine clinical practice. We identified an equal number of new users (n?=?182) of a candesartan/amlodipine (8/5?mg/day) FDC tablet (CAN/AML users) and a propensity-score matched cohort (n?=?182) receiving an olmesartan/azelnidipine (20/16?mg/day) FDC tablet (OLM/AZ users). Generalized estimating equations were used to estimate and compare the effects of the drugs on serum levels of creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid, sodium, potassium, aspartate aminotransferase, and alanine aminotransferase levels up to 12 months after the start of study drug administration. There was a significant increase of serum creatinine level and a significant decrease of eGFR from the baseline period to during the exposure period in both CAN/AML and OLM/AZ users, and a significant increase of BUN level in CAN/AML users. However, there were no significant differences in the mean changes of laboratory parameters between CAN/AML and OLM/AZ users. Our findings suggested that the effects of CAN/AML and OLM/AZ on laboratory parameters, including an unfavorable effect on renal function, were similar at least during 1 year of administration.     

Anti-inflammatory and metabolic effects of candesartan in hypertensive patients

BACKGROUND: Angiotensin II type 1 (AT1) receptor blocker therapy prevented or retarded the progression of coronary heart disease. The mechanisms of this benefit may relate to the ability of AT1 receptor blockers to reduce inflammation and insulin resistance. METHODS: We administered placebo or candesartan 16 mg daily during 2 months to 45 patients with mild to moderate hypertension. This study was randomized, double-blind, placebo-controlled, crossover in design. RESULTS: Candesartan therapy significantly lowered both systolic and diastolic blood pressure. Compared with placebo, candesartan therapy significantly lowered plasma hsCRP levels relative to baseline measurements from 1.10 to 0.70 mg/l (P=0.024) and soluble CD40 ligand levels by 30+/-11% (P<0.001). There were significant inverse correlations between body mass index and baseline plasma adiponectin levels (r=-0.480, P=0.009). There were significant correlations between baseline adiponectin levels and baseline insulin (r=-0.317, P=0.034) or baseline Quantitative Insulin-Sensitivity Check Index (QUICKI), a surrogate index of insulin sensitivity (r=0.371, P=0.012). Compared with placebo, candesartan therapy significantly lowered fasting insulin levels (P=0.011) and increased plasma levels of adiponectin by 15+/-4% (P=0.012) and increased QUICKI by 8+/-2% (P=0.007). There were significant correlations between percent changes in adiponectin levels and percent changes in insulin (r=-0.340, P=0.022) or QUICKI (r=0.325, P=0.029). CONCLUSIONS: Candesartan therapy significantly reduced inflammation and increased adiponectin levels and improved insulin sensitivity in hypertensive patients.     

坎地沙坦和苯那普利治疗高血压病的对照研究

目的评价坎地沙坦同苯那普利治疗高血压病的疗效及其对血脂、肾功能的影响及副作用。方法坎地沙坦组59例给予坎地沙坦剂量816 mg/d,苯那普利组56例服用苯那普利,剂量1020 mg/d,均治疗6周。治疗前后所有参与者测血压和测定胆固醇、三酰甘油、肾功能。结果监测血压显示坎地沙坦组降压与苯那普利组无差异,对胆固醇、三酰甘油没有影响,有降低尿酸的作用,与苯那普利组相比,咳嗽发生率低,并能改善肾功能及保护内皮细胞功能。结论坎地沙坦同苯那普利治疗轻、中度高血压病安全、有效,对血脂、肾功能无影响。坎地沙坦有降低尿酸的作用,咳嗽发生率低。     

Apoprotein B quantification in rhesus and cynomolgus monkey atherosclerotic lesions

The concept that much of the cholesterol deposition in atherosclerotic plaque development is provided by ingress of blood-derived apo B-rich lipoproteins into the arterial intima is given support by the study of arterial apo B accumulation. To compare the arterial wall level of immunoreactive apo B during the progression of diet-induced atherosclerosis in two widely used animal models of atherosclerosis, rhesus and cynomolgus monkeys were fed an atherogenic diet for 4, 8, and 12 months and their abdominal aortas quantitated for apo B. Apo B was extracted from aortic intima-media homogenates in two forms: Tris-buffer extractable or ‘loosely bound’ and detergent (Triton X-100) extractable or ‘tightly bound’. The aortic extracts were quantitated for apo B by radial immunodiffusion, using goat antirhesus apo B along with serum LDL standards of the appropriate species diluted in the two extract solutions.

The control monkeys' aortas contained only buffer-extractable apo B. The atherosclerotic aortas of both species of monkeys progressively increased their levels of loosely bound and tightly bound apo B through 4, 8, and 12 months of atherogenic diet feeding, with the 8- and 12-month cynomolgus aortas containing much larger amounts of apo B than the rhesus aortas. These differences in aortic apo B content could be accounted for by the greater rate at which the cynomolgus atherosclerotic lesions developed at the later time points. When the total lesion apo B levels were correlated with representative morphometrically-quantitated histopathologic sections of the homogenized aortas, a highly significant correlation was seen between the total aortic apo B values and both the absolute area of the intimal lesions and the total area of oil red O stainable lipid in the lesions (P < 0.001). These data indicate that as atherosclerotic lesions become larger and richer in lipid with progression of the disease, the amount of apo B-associated lipoproteins which are deposited unmetabolized in the lesions increases. These lipoproteins are increased in both the tightly bound and loosely bound forms.