Calcium metabolism, calcium-channel blocking agents, and hypertension management

Increasing evidence has suggested that a disturbance of cellular calcium metabolism may have a role in initiating and maintaining elevated systemic vascular resistance in essential hypertension. Controversy exists over whether calcium can alleviate or exacerbate the hypertensive process, and diversity of calcium metabolism in hypertensive patients has been proposed. Calcium-channel blocking agents are potent vasodilators capable of correcting the elevated systemic vascular resistance. Clinical studies have shown that these drugs have antihypertensive efficacy comparable to established agents. The elderly, blacks, and patients with low renin activity respond well to calcium-channel blockers. These drugs may also offer potential advantages over established antihypertensive agents in patients with other coexisting diseases. Sustained release formulations have been developed, and initial experience with long-term efficacy and tolerability is encouraging. The calcium-channel blockers may become first-line therapy for treatment of hypertension in selected patients.     

Clinical trials and tribulations

1. Pharmacologists should be involved in all stages of drug development. Often neglected is the final step, the clinical trials and other studies that determine clinical utility. The present article illustrates how pharmacoepidemiology can facilitate evaluation of the clinical potential of different drugs used to treat hypertension. 2. The evidence base for the drug treatment of hypertension is very strong. Large-scale outcome trials, largely based on diuretics, indicate that stroke events are prevented to the extent expected from blood pressure reduction, but there appears to be a shortfall in the prevention of coronary heart disease events. 3. On theoretical grounds, newer agents may be expected to have benefits in coronary heart disease prevention beyond blood pressure reduction. Recent trials with angiotensin-converting enzyme inhibitors and calcium channel blockers suggest no advantage over conventional drugs, but shortcomings in these studies mean that each is uninformative. 4. Observational studies based on pharmacoepidemiological principles offer an alternative approach to evaluating outcomes in treated hypertensives. 5. Evidence from the Glasgow Blood Pressure Clinic database suggest that there are outcome differences between antihypertensive agents. Angiotensin-converting enzyme inhibitor treatment is associated with a mortality advantage, whereas calcium channel blocker therapy is associated with a poorer prognosis. Preliminary findings from a primary care database support these observations. 6. Long-term follow up of a well-documented high-risk clinical population may allow detection of outcome differences not apparent in relatively short-term clinical trials. 7. Appropriate interpretation of observational data necessitates an understanding of the strengths and limitations of observational data. Clinical pharmacologists have a critical role in design and evaluation of pharmacoepidemiology studies.     

Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff

The role of beta-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, beta-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension. Although these agents lower blood pressure measured conventionally over the brachial artery with a blood pressure cuff, they do not exert a commensurate effect on blood pressure in the central aorta. Central aortic blood pressure and aortic augmentation index are strong predictors of left ventricular hypertrophy, an independent risk factor for cardiovascular events. Emerging data are illuminating the antihypertensive paradox whereby antihypertensive agents may elicit discordant effects on central and peripheral blood pressure and hemodynamics. Vasodilatory antihypertensives, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, elicit reductions in central aortic blood pressure equal to or greater than that in the brachial artery. Conversely, beta-blockers lower central aortic blood pressure to a lesser degree even when blood pressure measured by sphygmomanometry is reduced substantially. Given the strong relationship between central aortic blood pressure and target organ damage, the effectiveness of beta-blockers may be overestimated in practice on the basis of conventional blood pressure measurements alone. Differences in central and peripheral blood pressure may account for the lack of cardiovascular protection afforded by beta-blockers in clinical trials and could account for a portion of the apparent "benefit beyond blood pressure" reduction with other classes of antihypertensive agents. Future studies should aim to better clarify the role of central aortic blood pressure in the treatment of hypertension. In the meantime, the effects of antihypertensive drugs on blood pressure "beyond the brachial blood pressure cuff" should be considered when prescribing antihypertensive agents for a patient.     

Can the renin-angiotensin system protect against stroke? A focus on angiotensin II receptor blockers

From a patient's perspective, stroke is the most devastating form of cardiovascular disease, representing the number one cause of permanent disability in the United States. Treatment of hypertension significantly reduces the risk of stroke; however, it is unclear whether all antihypertensive agents are equivalent in this regard. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the risk of cardiovascular events, including stroke. Although attenuation of the renin-angiotensin system (RAS) is often credited with the blood pressure-independent effects of this class of agents, this hypothesis has not been confirmed with regard to the end point of stroke. In fact, drugs that activate the RAS, such as diuretics and dihydropyridine calcium channel blockers, are as effective or superior to ACE inhibitors for stroke prevention. Angiotensin II receptor blockers (ARBs) selectively block the angiotensin II subtype I receptor, which results in a reflexive increase in levels of angiotensin II and unopposed activation of angiotensin II subtype 2 receptors. Clinical trials comparing ARBs with active controls have reported significant reductions in stroke in ARB-treated patients. Data on ARBs and other drugs that activate the RAS (diuretics and dihydropyridine calcium channel blockers) support a potential role for the RAS in protecting against stroke. Ongoing trials with ARBs are evaluating stroke as a primary end point, and results should help to further elucidate the role of ARBs in this disease. Until then, it is prudent to treat hypertension with an agent or combination of agents that are likely to result in a rapid and sustained reduction in blood pressure, taking into consideration patient characteristics, comorbidities, tolerability, and cost.     

Calcium channel blockers in the spectrum of antihypertensive agents

Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Through blood pressure reduction, and possibly other mechanisms such as antioxidative effects, they may play a role in diminishing the risk for a variety of cardiovascular outcomes. The combination of CCBs with other newer antihypertensive agents such, as ACE inhibitors and angiotensin receptor blockers, may provide complementary effects on risk reduction in cardiovascular adverse events and renal disease. Although the efficacy of CCBs as antihypertensive agents has been adequately demonstrated, there have been concerns regarding the use of short acting dihydropyridines after acute myocardial infarction. There have also been questions about the role of CCBs with regards to other antihypertensive agents in renal disease. For example, differential effects of dihydropyridine and non-dihydropyridine CCBs may affect progression of renal disease and risk for diabetes. Certain precautions involving drug interactions are needed because of the effects of CCBs on the CYP450 enzyme systems.     

Calcium channel blockers in the spectrum of antihypertensive agents

Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Through blood pressure reduction, and possibly other mechanisms such as antioxidative effects, they may play a role in diminishing the risk for a variety of cardiovascular outcomes. The combination of CCBs with other newer antihypertensive agents such, as ACE inhibitors and angiotensin receptor blockers, may provide complementary effects on risk reduction in cardiovascular adverse events and renal disease. Although the efficacy of CCBs as antihypertensive agents has been adequately demonstrated, there have been concerns regarding the use of short acting dihydropyridines after acute myocardial infarction. There have also been questions about the role of CCBs with regards to other antihypertensive agents in renal disease. For example, differential effects of dihydropyridine and non-dihydropyridine CCBs may affect progression of renal disease and risk for diabetes. Certain precautions involving drug interactions are needed because of the effects of CCBs on the CYP450 enzyme systems.     

Dihydropyridine calcium channel antagonists in the management of hypertension

Dihydropyridine calcium channel antagonists have been maligned in recent years because of concerns regarding their cardiovascular and overall safety profile. Specifically, it was widely publicised in the mid-1990s that these agents might increase the risk of myocardial infarction, gastrointestinal bleeding and cancer. Data linking these agents with increased cardiovascular risk were based on nonrandomised studies and implicated short-acting, immediate-release agents. These results were inappropriately extrapolated to longer-acting compounds, extended-release products, and to the non-dihydropyridine class. Fortunately, recent studies have vindicated the class from safety allegations. These studies are reviewed herein. Compared with both diuretics and contemporary agents, amlodipine decreases cardiovascular events to a similar or greater extent without evidence for increased coronary heart disease, gastrointestinal bleeding or cancer. Despite these data, initial concerns have had lasting repercussions, as the use of dihydropyridine calcium channel antagonists appears to lag behind what emerging data would support. Dihydropyridine calcium channel antagonists have several noteworthy attributes that merit consideration in the management of hypertension. The blood pressure response to this class of drugs is less contingent on patient factors such as age and race compared with other antihypertensive agents (e.g. ACE inhibitors). Dihydropyridine calcium channel antagonists may exert effects that protect against stroke that are independent of their blood pressure-lowering mechanism. Unlike diuretics and beta-adrenoceptor anatagonists (beta-blockers), dihydropyridine calcium channel antagonists are lipid neutral and do not disturb glucose homeostasis. Dihydropyridine calcium channel antagonists demonstrate a highly desirable profile when administered as part of combination therapy. Combinations of dihydropyridine calcium channel antagonists and ACE inhibitors or angiotensin receptor antagonists display additive efficacy and an enviable adverse-effect profile. Collectively, the cardiovascular benefit, metabolic neutrality and homogeneous blood pressure response illuminated in recent studies, and reviewed here, represent a reaffirmation of the benefit of long-acting dihydropyridine calcium channel antagonists and should serve to help reinforce the critical importance of these agents in the therapeutic armamentarium against cardiovascular disease.     

Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension

Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs.     

Calcium Channel Antagonists in the Treatment of Hypertension

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations — which had by then become generic and inexpensive — retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and β-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.     

Antihypertensive therapy in the geriatric patient. I: A review of the role of calcium channel blockers

Animal and clinical studies have demonstrated the efficacy of calcium channel blockers in reducing blood pressure, especially in older patients whose hypertension is characterized by increased peripheral vascular resistance. Their chemical heterogeneity, which permits targeted therapy, as well as their minimal side effects, drug interactions, and clinical utility in numerous pathophysiologic states common to the elderly, enhance the suitability of calcium channel blockers in treating mild to moderate hypertension in this subgroup. This is particularly relevant for those patients who have concomitant conditions, such as diabetes, chronic obstructive pulmonary disease, or peripheral vascular disease, and for whom many of the more traditional antihypertensive drugs are either contraindicated or might cause a worsening of the disease.     

Pharmacological, immunological, and gene targeting of the renin-angiotensin system for treatment of cardiovascular disease

Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.     

Factors influencing hepatic metabolism of antihypertensive drugs: impact on clinical response

Introduction: Although main antihypertensive drugs are able to efficiently reduce blood pressure, only a third of treated hypertensive patients achieve optimal blood pressure control. Extensive interpatient variability on drug metabolism and oral disposition of blood pressure lowering drugs can contribute to this failure in hypertension management.

Areas covered: The aim of the present review is to update the knowledge on the features of hepatic metabolism of the main antihypertensive agents, including β-blockers, calcium channel blockers, angiotensin receptor blockers, and angiotensin converting enzyme inhibitors. The factors that contribute to the large interindividual variability of main antihypertensive drugs are also covered.

Expert opinion: The variability of plasma concentration of antihypertensive drugs due to the involvement of hepatic metabolism can contribute to the inadequate control of blood pressure in the daily clinical practice. Genotype screening of specific hepatic drug-metabolizing enzymes may contribute to optimize dose selection and to increase the rate of blood pressure control in patients treated with specific β-blockers, calcium channel blockers, and angiotensin receptor blockers.     

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.     

Antihypertensive drug therapy in patients with African ancestry

Blood pressure plays an important role in the development and progression of cardiovascular disease. Among hypertensive patients, those with African ancestry present with distinctive metabolic characteristics and cardiovascular profile. As a result, the need for individualized antihypertensive treatment strategy is of great importance. Lifestyle modifications as well as low sodium diet will play a major role in controlling blood pressure. The initiation of antihypertensive treatment with calcium channel blockers or diuretics is favored over angiotensin receptor blockers, angiotensin-converting enzyme inhibitors or β-blockers, provided no specific indications for the latter drugs are present. Moreover, the need for combination treatment often arises. As a result, the effective and safe hypertension management of patients with African ancestry is of critical importance for reducing cardiovascular morbidity and mortality.     

临床应用二氢吡啶类钙通道阻滞剂的循证医学评价

目的：评价二氢吡啶类钙通道阻滞剂（DHP—CCB）的临床应用进展,及其有效性和安全性。方法：搜集DHP—CCB临床应用相关的系统评价及大规模临床对照研究,对DHP—CCB和安慰剂或者其它药物进行比较,评价其有效性和安全性。结果：共检索到3项大型临床研究和20项系统评价,对DHP—CCB应用于高血压、心绞痛、蛛网膜下腔出血、抑制分娩等症状的有效性和安全性进行评价。结论：DHP—CCB在控制收缩压和舒张压上和其它药物效果相同,与其它降压药合用,效果和安全性更好。在老年单纯收缩期高血压患者,应用DHP—CCB明显降低肾功能不全和痴呆。DHP—CCB与β-受体阻滞剂合用于冠心病患者中,效果和安全性更好。DHP—CCB能够改善蛛网膜下腔出血预后。在抑制分娩中,DHP—CCB较其它抑制分娩药更有效,安全性更好。DHP—CCB应用于缺血性卒中的安全性和有效性尚待进一步的临床数据证实。     

Use of antihypertensive drugs in the Italian hospitals. GIFA group. Gruppo Italiano di Farmacoepidemiologia nell'Anziano.

Calcium channel blockers and ACE-inhibitors are among the most common drugs prescribed for the initial treatment of hypertension. While their ability to control surrogate outcomes, such as blood pressure and left ventricular hypertrophy, is proven, there is limited evidence of their prevention of major cardiovascular events, including mortality. The aim of our work was to assess the use of these drugs in Italy in comparison with beta-blockers and diuretics. We examined the consumption of the four main antihypertensive classes of drugs (beta-blockers, diuretics, calcium channel blockers and ACE- inhibitors). In-hospitalization data from the GIFA (Gruppo Italiano di Farmacoepidemiologia nell'Anziano) database were used. During the period from 1988 to 1995, the most frequently prescribed antihypertensive drugs were calcium channel blockers (47%) followed by diuretics (37%), ACE-inhibitors (33%) and beta-blockers (5.5%). Changes over time in the use of these drugs were analysed: ACE-inhibitors had the greatest increase in use over time. Calcium channel blockers, ACE-inhibitors and beta-blockers were usually prescribed to the youngest patients (aged <65 years), while diuretics to the oldest. Calcium channel blockers were prescribed to 60% of patients with myocardial infarction and to 55% of those with congestive heart failure. In conclusion, our study demonstrates that the Italian physicians very often prescribe drugs like calcium channel blockers and ACE-inhibitors. Among these pharmacological agents, enalapril (twice per day) and slow release calcium channel blockers are the most frequently prescribed drugs.     

How to use calcium antagonists in hypertension: putting the JNC-VI guidelines into practice. Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure.

The prevention and treatment of hypertension remain as major challenges for clinicians all over the world. The recently published Sixth Report of the Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) uses evidence-based medicine in providing guidelines to aid clinicians in the prevention, detection and treatment of high blood pressure, including pharmacological approaches. Calcium antagonists are used widely for the treatment of hypertension, and JNC-VI focuses on specific situations where calcium antagonists could be considered as preferred treatments. There are a large number of calcium antagonists available, with a variety of pharmacodynamic and pharmacokinetic actions. Several sustained-release formulations of these drugs are also available. In terms of blood pressure control, calcium antagonists are more effective as antihypertensive treatments than beta-blockers, ACE inhibitors and angiotensin II receptor blockers in Black patients. The dihydropyridine calcium antagonists have been shown to reduce morbidity and mortality in elderly patients with isolated systolic hypertension. The rate-lowering calcium antagonists can be used as alternatives to beta-blockers in patients with coronary artery disease and hypertension. Calcium antagonists can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus and/or renal disease. Some dihydropyridine calcium antagonists may be useful as alternatives to ACE inhibitors in patients with hypertension and systolic heart failure. Calcium antagonists appear to be extremely useful in patients with cyclosporin-induced hypertension, and in patients with hypertension and concomitant Raynaud's phenomenon and/or migraine. The rate-lowering agents can be used in patients with atrial tachyarrhythmias and hypertension. Clinicians should be aware of drug-drug interactions involving calcium antagonists, especially after the recent problems with mibefradil. Although retrospective studies have caused controversy regarding the safety of calcium antagonists in patients with hypertension, recent prospective studies have revealed no major safety concerns with these drugs.     

Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis.

We conducted a systematic review of randomized, controlled, monotherapy trials since 1990 of oral antihypertensive agents in patients with essential hypertension. Our objective was to quantify the frequency of discontinuation of antihypertensive agents due to adverse events from a meta-analysis of the studies. A total of 190 studies met inclusion criteria. The highest frequency of discontinuations due to adverse events (DAEs) occurred with calcium channel blockers (6.7%) and alpha-adrenergic blockers (6.0%); the lowest with diuretics and angiotensin receptor blockers (each 3.1%). Only in calcium channel blocker studies was the frequency of DAEs greater in treated patients than in patients receiving placebo, but the difference was not significant. This systematic review suggests that the frequency of DAEs in monotherapy antihypertensive trials varies across drug classes and should be considered when choosing drugs for patients with essential hypertension.     

Antihypertensive therapy and arterial function in experimental hypertension

• 1.1. Alterations in the function of the endothelium and arterial smooth muscle may be important in the establishment of hypertension. Thus, the possible favorable influences of blood pressure-lowering agents on vascular responsiveness may be important in the chronic antihypertensive actions of these compounds.
• 2.2. A number of reports have suggested that ACE inhibitors can improve arterial function in hypertension, whereas the knowledge about the vascular effects of other antihypertensive drugs, like β-blockers, calcium channel blockers, and diuretics remains rather limited.
• 3.3. In this article, the effects of antihypertensive therapy on arterial function in human and experimental hypertension are reviewed.