Nicardipine, a new calcium channel blocker: role for vascular selectivity

Calcium channel blockers are important drugs for the treatment of chronic stable angina. However, negative inotropic and dromotropic effects may limit their usefulness in patients with atrioventricular conduction abnormalities or left ventricular dysfunction. A new generation of calcium channel blockers will soon be available that have a more vascular selective action than currently available agents. Of the new agents, nicardipine has been most extensively studied. In experimental studies, nicardipine is more specific for vascular smooth muscle than for cardiac smooth muscle and for coronary than peripheral vasculature. In controlled trials, nicardipine exhibited efficacy and safety that was comparable to older calcium blockers or beta blockers. However, nicardipine was associated with minimal negative inotropic or dromotropic effects even in patients with existing left ventricular dysfunction. Thus, nicardipine may have an advantage over existing calcium channel blockers, especially in patients with underlying cardiac disease.     

Hypertension and sudden death. Disparate effects of calcium entry blocker and diuretic therapy on cardiac dysrhythmias

This study was designed to evaluate the impact of antihypertensive therapy on cardiac dysrhythmias in 13 hypertensive patients who received calcium entry blockers and in 10 hypertensive patients who received hydrochlorothiazide. Mean arterial pressure fell to a similar extent in both treatment groups; however, left ventricular mass index decreased (from 102 +/- 4 to 95 +/- 2 g/m2) only in patients receiving calcium entry blockers, but not in those taking hydrochlorothiazide. The prevalence of premature ventricular contractions decreased 74% from 21 +/- 14/h to 5.7 +/- 6/h in the calcium entry blocker group, but did not change in the hydrochlorothiazide group (15 +/- 17/h to 16 +/- 13/h). Couplets, multiform contractions, ventricular tachycardia, and supraventricular tachycardia were completely abolished after calcium entry blocker therapy, whereas the prevalence of these arrhythmias remained unchanged during treatment with hydrochlorothiazide. We conclude that antihypertensive therapy with calcium entry blockers (but not with thiazide diuretics) reduces left ventricular mass and the prevalence and severity of ventricular dysrhythmias. Whether this reduction will improve the ominous prognosis of left ventricular hypertrophy and diminish the risk of sudden death remains unknown.     

Risk Reduction Following Regression of Cardiac Hypertrophy

Cardiac hypertrophy in essential hypertension is documented to be an independent risk factor for congestive heart failure, coronary heart disease and cardiac sudden death. Reduction of left ventricular hypertrophy therefore emerged as a new challenge of antihypertensive treatment. Sympatholytic agents, calcium entry blockers, and angiotensin converting enzyme inhibitors have been found to reduce left ventricular hypertrophy, whereas vasodilators (and most likely also diuretics) are unable to reduce left ventricular mass despite good control of arterial hypertension. Several studies indicated that reduction of left ventricular hypertrophy is not detrimental to cardiac pump function: systolic and diastolic function were found to be maintained at rest and during exposure to increased pressure load. In hypertensive patients with left ventricular hypertrophy ventricular arrythmias have been reported to be increased and to be the pathophysiological link for the increased risk of cardiac sudden death. Reduction of cardiac hypertrophy was found to be accompanied by a reduction of prevalence and severity of ventricular arrhythmias if treated with betablockers, calcium entry blockers or converting enzyme inhibitors. Whether reduction of cardiac hypertrophy indeed decreases the cardiovascular risk attributed to left ventricular hypertrophy is unknown at present, although clinical studies support such a viewpoint.     

Individualization of Therapy for Hypertension in the 1990′S: The Role of Calcium Antagonists

The Joint National Committee Reports IV 1988 and V 1992 have emphasized individualization of drug therapy for patients with hypertension - a departure from the “stepped” care approach of initiating therapy with diuretics as advocated by the JNC I-III in the 1970′s and 1980′s. This review highlights individualization or “patient profiling” using calcium channel blockers as first-line treatment strategy for patients with primary hypertension - especially in the patient who has attendant risk factors and sequelae. The calcium channel antagonists, especially effective in elderly and Black patients, have proven efficacy in reducing left ventricular hypertrophy and improving diastolic function in patients with hypertensive heart disease. The heart rate limiting calcium antagonist, verapamil, has been found effective in outcome trials of reducing death and reinfarction rates post myocardial infarction and is an alternative therapy for the beta blocker intolerant hypertensive post myocardial infarction. More vascular specific dihydropyridines (felodipine, isradipine, and amlodipine) may be preferable to rate limiting agents in hypertensives with sinus node or AV conduction disorders and in those with impaired left ventricular systolic function. Verapamil and diltiazem have been affective in preliminary trials in reducing proteinuria and preserving renal function in both diabetic and non diabetic hypertensives. Calcium channel antagonists appear to prevent the progress of atherosclerosis independent of their antihypertensive properties.

Further, they have theoretic value in improving endothelial mediated vasodilation.     

Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress.

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.     

Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.     

Efficacy and safety of calcium channel blockers in hypertensive patients with concomitant left ventricular dysfunction.

The use of calcium channel blockers (CCBs) in the treatment of hypertension and concomitant left ventricular dysfunction is reviewed. Some CCBs, particularly second-generation dihydropyridine agents such as felodipine, isradipine, nicardipine, nimodipine, and nitrendipine, have properties that enhance their usefulness in these patients. All CCBs have a similar mechanism of action. Differences in their selective action at various tissue sites determine which are most appropriate for patients with concomitant hypertension and left ventricular dysfunction. Most CCBs do not produce reflex stimulation of the heart or induce intravascular expansion. While all CCBs produce arteriolar dilation, all local beds and regional circulations in target organs are not affected equally. Most CCBs can decrease cardiac mass, and second-generation CCBs tend to have little or no negative inotropic effects at therapeutic dosages. In addition, they increase blood flow and reduce myocardial oxygen requirements. Because of differences in functional and electrophysiologic effects, specific CCBs may not be appropriate for all patients. Since second-generation dihydropyridine CCBs lack clinically relevant negative inotropic effects, and have been shown to improve exercise tolerance and coronary artery perfusion, they are appropriate for hypertensive patients with left ventricular dysfunction, angina, and coronary heart disease. Second-generation CCBs tend to lack cardiodepressant side effects and are less likely to react with digoxin than are first-generation CCBs.     

Eplerenone: A Selective Aldosterone Blocker

Recent studies suggest that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease. Some of the adverse cardiovascular effects that have been described include cardiac and vascular fibrosis, vascular necrosis and inflammation, impaired endothelial function, reduced fibrinolysis, hypertension, left ventricular hypertrophy (LVH), congestive heart failure, and cardiac arrhythmias. In light of these findings, the ability to block the actions of aldosterone has gained increased therapeutic importance. Eplerenone is a selective aldosterone receptor blocker that displays little interaction with androgen and progesterone receptors. Eplerenone has already been approved for the treatment of systemic hypertension and has been evaluated in numerous hypertension subgroups, including patients with low plasma renin activity; diabetes; LVH; uncontrolled blood pressure while receiving monotherapy with angiotensin‐converting enzyme inhibitors, angiotensin‐receptor blockers, calcium channel blockers, or beta‐blockers; and in black patients. Results of these trials indicate that eplerenone lowers blood pressure and reduces end‐organ damage. Further proof of the therapeutic importance of mineralocorticoid receptor blockade comes from the eplerenone post acute myocardial infarction survival and efficacy study (EPHESUS). In this large‐scale clinical outcome trial, eplerenone was shown to reduce total mortality by 15% as well as the combined endpoint of cardiovascular mortality/cardiovascular hospitalization by 13% when administered at a mean of 7.3 days post myocardial infarction to patients with evidence of systolic left ventricular dysfunction and symptoms of heart failure. Eplerenone is well tolerated, with an adverse effect profile comparable to placebo. The advent of selective aldosterone blockers, such as eplerenone, should prove to be of great therapeutic value in hypertension control and prevention of cardiovascular disease and associated end‐organ damage.     

Left ventricular unloading with calcium antagonists

Calcium channel blockers reduce the arterial smooth muscle tone and lower blood pressure. They may be regarded as left ventricular unloading agents. Left ventricular unloading efficacy of nifedipine (15 cases) and verapamil (14 cases) was tested in hypertensive decompensated patients, through one-month treatment period. Nifedipine persistently reduced systemic vascular resistance, mean arterial pressure, mean pulmonary wedge pressure and left ventricular diastolic diameter and improved cardiac index and velocity of circumferential fiber shortening. All of the patients had relief from dyspnea and reduction in heart size. The only side effect was ankle edema in 6 cases. Verapamil reduced systemic vascular resistance and mean arterial pressure and was not effective on mean pulmonary wedge pressure, left ventricular diastolic diameter and velocity circumferential fiber shortening. The drug was discontinued in 2 patients who developed severe dyspnea at rest after a 3-4 day continued oral treatment. Clinical symptoms and signs did not improve in the remaining subjects despite persistent pressure reduction. A less potent vasodilating action of verapamil and a prominent depression in cardiac contractility may account for the different results with the two compounds, in spite of a shared vasodilating antihypertensive effect. These findings prove that functional changes in the failing hypertensive heart may differ from one calcium blocker to another as a result of interaction and relative preponderance of influences on afterload and contractility.     

Effects of obesity and subsequent weight reduction on left ventricular function

Obesity is reaching epidemic proportions in the United States. Obesity adversely affects the circulatory system with resultant endothelial dysfunction, which promotes systemic hypertension, coronary artery disease, and vascular calcification. It is believed that the release of adipokines is responsible for this effect. In addition, obesity causes intrinsic changes in the heart including an increase in left ventricular (LV) mass, LV hypertrophy, LV dilatation, left atrial dilatation, and diastolic, as well as systolic dysfunction in some cases. The combination of increased adipose cells and an increase lean muscle mass in obese patients results in high cardiac output and an accompanying increased circulating volume leading to these adaptive changes. Weight loss by means of caloric restriction or surgery results in favorable hemodynamic changes referred to as "reverse remodeling." Regression of LV mass and chamber size has been shown universally. However, some studies have failed to reveal improvement in diastolic function possibly because of confounders such as nutritional deficiency that may occur after weight loss surgery. Some evidence seems to suggest that the greatest regression of LV mass and LV hypertrophy may occur when weight loss is combined with beta-adrenergic blocker therapy (in those who have an indication for the drug) when compared with other antihypertensive drugs versus weight loss alone.     

Influence of early antihypertensive treatment on vascular and cardiac design in SHR with and without renal hypertension.

The present study was designed to explore to what extent pressure reduction by antihypertensive therapy and pressure elevation by renal hypertension are able to affect structural vascular and cardiac changes in young spontaneously hypertensive rats (SHR). Pressure elevation in SHR was induced by means of superimposing 2 kidney, 1 clip renal hypertension (2K1C). Pressure reduction was achieved by means of the vasoselective calcium antagonist felodipine from 6 to 13 weeks of age in both clipped and unclipped SHR. Vascular structure of the skeletal muscle was assessed hemodynamically by perfusing a hindlimb preparation and left ventricular dimensions were calculated from pressure-volume relationships of isolated hearts arrested in diastole. Induction of renal hypertension in SHR resulted, besides augmentation of arterial pressure in a marked concentric left ventricular hypertrophy, i.e. elevations of wall thickness to internal radius ratio. Likewise, in renal hypertensive SHR, a structural adaptation of the skeletal muscle vascular bed occurred, reflected as elevations of minimal vascular resistance and maximal generated perfusion pressure. Antihypertensive treatment for 8 weeks with felodipine reduced and also prevented mean arterial pressure from increasing further in SHR, and in SHR with superimposed renal hypertension by approximately 15% (p < 0.001 for both). In renal hypertensive SHR, felodipine partly prevented the development of exaggerated structural changes, both in the heart and in the skeletal muscle vascular bed, as reflected by reduced wall thickness to internal radius ratio and reduced minimal vascular resistance by 22% and maximal pressure response by 10% respectively (p < 0.01 for both parameters).(ABSTRACT TRUNCATED AT 250 WORDS)     

Managing the elderly patient with both hypertension and pulmonary disease

Older patients with both hypertension and pulmonary disease pose a challenge to the physician. Satisfactory blood-pressure control must be achieved without exacerbating the concomitant pulmonary disease. Diuretics may interfere with mucus production and cause acid-base and electrolyte abnormalities. The beta-adrenergic blocking agents should be avoided because of their risk of inducing bronchospasm. If a beta blocker must be used, it should be combined with an alpha- and beta-adrenergic blocker, or an agent with intrinsic sympathomimetic activity or beta 1 selectivity. The direct and indirect vasodilators may be used safely in these patients, but the risk of worsening any underlying coronary artery disease must be kept in mind when prescribing either hydralazine or minoxidil. The calcium channel blockers and ACE-inhibitors have the best safety record in treating the elderly who have hypertension and COPD. For these patients, the calcium channel blockers offer the advantage of simultaneous therapy of coronary artery disease, whereas hypertensive patients with congestive heart failure would be more likely to benefit from an ACE-inhibitor. The ability to treat hypertension without precipitating unwanted adverse reactions or dangerous side effects is one of the arts of medicine. Fortunately, the range of drugs available to today's physician allows safe and efficacious treatment of the elderly patient who has both hypertension and pulmonary disease.     

Combination therapy with calcium-channel blockers and beta blockers for chronic stable angina pectoris

Combination therapy using calcium-channel blockers and beta blockers in patients with refractory chronic stable angina has gained much popularity, but remains highly controversial because of the potential for serious additive deleterious hemodynamic or electrophysiologic reactions. In studies involving patients with preserved left ventricular function receiving chronic oral beta blockers, short-term administration of intravenous verapamil has been shown to cause a further lowering in heart rate and blood pressure while prolonging atrioventricular node conduction; additive cardiodepressant effects were noted, including a tendency toward increased left and right heart filling pressures. Nifedipine, on the other hand, when added acutely to beta blockers, causes an increase in heart rate, a decrease in blood pressure and either no change or a slight improvement in most cardiac performance variables. Controlled, double-blind clinical trials have demonstrated that combinations of calcium-channel blockers and beta blockers result in augmented symptom benefit compared with either drug class alone. The predominant mechanism responsible for such improvement is increased lowering of myocardial oxygen demand by virtue of additive diminution in heart rate, blood pressure and, consequently, pressure-rate product both at rest and during exercise. Verapamil (and possibly diltiazem) plus beta blockers appears to have the greatest therapeutic efficacy but also the highest frequency of harmful adverse cardiac effects, whereas nifedipine plus beta blockers is generally safer but also less efficacious. Factors that should be carefully considered by clinicians contemplating combination therapy are the choice of calcium-channel blocker, the dose of calcium-channel blocker and beta blocker, the presence of antecedent left ventricular dysfunction or conduction system disease and the possibility of drug interactions. Concomitant calcium-channel blocker and beta-blocker therapy is an important contribution to the pharmacologic management of resistant patients who remain symptomatic during single drug treatment. However, the possibility of additive adverse cardiac effects mandates careful patient selection and close clinical monitoring.     

Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction

OBJECTIVES: The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction. BACKGROUND: Increased conduit vessel stiffness increases pulse pressure and pulsatile load, potentially contributing to adverse outcomes in patients with left ventricular dysfunction. METHODS: Pulse and mean arterial pressure were analyzed for their effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 6,781 patients randomized into the Studies of Left Ventricular Dysfunction trials. RESULTS: Pulse and mean arterial pressure were related positively to each other, age, ejection fraction and prevalence of diabetes and hypertension and inversely to prior myocardial infarction and beta-adrenergic blocking agent use. Higher pulse pressure was associated with increased prevalence of female gender, greater calcium channel blocking agent, digoxin and diuretic use, lower heart rate and a higher rate of reported smoking history. Higher mean arterial pressure was associated with higher heart rate, lower calcium channel blocker and digoxin use and lower New York Heart Association functional class. Over a 61-month follow-up 1,582 deaths (1,397 cardiovascular) occurred. In a multivariate analysis adjusting for the above covariates and treatment assignment, higher pulse pressure remained an independent predictor of total and cardiovascular mortality (total mortality relative risk, 1.05 per 10 mm Hg increment; 95% confidence interval, 1.01 to 1.10; p = 0.02). Mean arterial pressure was inversely related to total and cardiovascular mortality (total mortality relative risk, 0.89; 95% confidence interval, 0.85 to 0.94; p <0.0001). CONCLUSIONS: One noninvasive blood pressure measurement provides two independent prognostic factors for survival. Increased conduit vessel stiffness, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure.     

Hochdruckherz und hypertensive Mikroangiopathie

Cardiac alterations in patients with arterial hypertension comprise the manifestation of stenosis in epicardial arteries, disease of coronary resistive vessels, prothrombotic changes and endothelial dysfunction, pronounced perivascular and interstitiell fibrosis, left ventricular hypertrophy, dilatation of the left atrium, increased sympathetic drive and degeneration of aortic valve. These alterations leads to the major clinical manifestations of hypertensive heart disease, that are symptoms of reduced coronary conductance, left ventricular hypertrophy, diastolic and systolic dysfunction with or without left ventricular enlargement and arrythmia. Different non-inavsive and invase procedures are available for screening and follow up of patients with hypertensive heart disease. The primary therapeutic target is, apart from lowering blood pressure, to reverse cardiac manifestations of arterial hypertension using specific therapeutic algorithms.     

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.     

Managing the hypertensive patient with ischemic heart disease

Thiazide diuretics, b-blockers, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors are all superior to placebo for the primary prevention of coronary events in patients with hypertension. Recent studies have shown that ACE inhibitors are better than other antihypertensive agents in lowering overall cardiovascular morbidity and mortality, especially stroke. Blood pressure should be aggressively lowered (to < 140/90 mm Hg), especially in diabetic patients (to < 130/80 mm Hg), but care should be exercised in lowering the diastolic blood pressure below 65 mm Hg in patients with significant occlusive coronary artery disease. Hypertension in patients with stable angina should be treated with a b-blocker (alternatively a calcium channel blocker) together with an ACE inhibitor. Patients with hypertension and acute coronary syndrome (unstable angina or myocardial infarction) should be treated with a b-blocker, and with an ACE inhibitor if there is left ventricular dysfunction. A thiazide diuretic and/or a dihydropyridine calcium channel blocker could be added for blood pressure control. Calcium channel blockers should be avoided if there is significant left ventricular dysfunction.     

Hypertensive heart disease and microangiopathy

Cardiac alterations in patients with arterial hypertension comprise the manifestation of stenosis in epicardial arteries, disease of coronary resistive vessels, prothrombotic changes and endothelial dysfunction, pronounced perivascular and interstitial fibrosis, left ventricular hypertrophy, dilatation of the left atrium, increased sympathetic drive and degeneration of aortic valve. These alterations leads to the major clinical manifestations of hypertensive heart disease, that are symptoms of reduced coronary conductance, left ventricular hypertrophy, diastolic and systolic dysfunction with or without left ventricular enlargement and arrhythmia. Different non-invasive and invase procedures are available for screening and follow up of patients with hypertensive heart disease. The primary therapeutic target is, apart from lowering blood pressure, to reverse cardiac manifestations of arterial hypertension using specific therapeutic algorithms.     

Hemodynamics of nicardipine in coronary artery disease

Calcium antagonists influence cardiovascular hemodynamics by 3 actions: peripheral arterial dilatation, coronary arterial dilatation and negative inotropic effect. The net hemodynamic effects vary depending on the relative strength of each action. Intravenous administration of the new compound nicardipine, a dihydropyridine derivative with calcium antagonist activity that is chemically related to nifedipine, induced a marked reduction of systemic vascular resistance in patients with and without β blockade. This was accompanied by an increase in cardiac output and left ventricular ejection fraction. In addition, end-diastolic pressure, peak (+) dP/dt and dP/dt measured at a developed pressure of 40 mm Hg and normalized for this pressure remained unchanged. The time constant of isovolumetric pressure drop during the first 40 ms also decreased. Intravenous administration of nicardipine prevented a marked increase in end-diastolic pressure during exercise, and augmented left ventricular ejection fraction in chronic heart failure. At doses producing similar increases in coronary sinus blood flow, intracoronary administration of nicardipine, unlike nifedipine, has little effect on left ventricular contractility and end-diastolic pressure. Nicardipine is a powerful systemic vasodilator with minimal effects on myocardial inotropic state, even in patients with compromised left ventricular function and patients receiving β blocker therapy.     

Disparate hemodynamic responses to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers

The hemodynamic response to mental challenge was studied in 40 male outpatients with mild essential hypertension. The patients were treated randomly either with a beta adrenoreceptor blocker (oxprenolol) or with a calcium entry blocker (nitrendipine). Cardiovascular reactivity was evaluated with two different mental arithmetic tasks before and six months after treatment by continuously measuring systolic and diastolic pressure (ultrasonic Doppler device), heart rate (electrocardiography), and stoke volume (impedance cardiography). Patients in both treatment groups had equal decreases in arterial pressure and the same pressures at rest. In patients receiving calcium entry blockers, mental challenge provoked an increase in stroke volume and a decrease in total peripheral resistance similar to results in the pretreatment phase. In contrast, beta adrenoreceptor blockade reversed the hemodynamic response pattern to a distinct decrease in stroke volume (p less than or equal to 0.05) and an increase in total peripheral resistance (p less than or equal to 0.05). In addition, an attenuated heart rate response (p less than or equal to 0.01) and a larger increase in diastolic pressure (p less than or equal to 0.01) were found in the beta blocker group compared with the calcium entry blocker group. Although beta blockers and calcium blockers produce equal decreases in arterial pressure, beta blockers evoke an abnormal hemodynamic response to mental challenge, whereas calcium entry blockers preserve the physiologic reactivity pattern of the untreated state.