Effects Of Celiprolol Research Articles

Effects of Celiprolol and Bisoprolol on Blood Pressure, Vascular Stiffness, and Baroreflex Sensitivity

We tested the hypothesis that celiprolol and bisoprolol have differential effects on blood pressure (BP), flow-mediated dilation (FMD), and vascular stiffness. We analyzed 102 hypertensives (mean age: 59±14 years) who were being treated other than beta-blockers. They were randomized to receive add-on treatment with either celiprolol 100-200mg (C group) or bisoprolol 2.5-5mg (B group), and followed up for 3 months. In addition to clinic, home, and ambulatory BP monitoring, the FMD, radial augmentation index (AI), brachial-ankle pulse wave velocity (baPWV), urine albumin-to-creatinine ratio, and baroreflex sensitivity (BRS) were measured at baseline and at the end of the study. Compared to the baseline values, home and 24-hour BP were significantly lowered in the third month in both groups (all Ps < 0.05). Pulse rate (PR) and baPWV were reduced (P < 0.001), and BRS was increased significantly only in the B group (P = 0.02). Radial AI was unchanged in the C group but was significantly increased in the B group (P < 0.001). Central BP was significantly reduced in the C group (P = 0.003) but was unchanged in the B group. FMD was significantly increased in both groups (both P < 0.01). Bisoprolol achieved the greater reduction of PR and improved BRS and vascular stiffness, whereas, celiprolol reduced the central BP level. In treated hypertensive patients, add-on use of celiprolol may be favorable in uncomplicated stage of hypertension. On the other hand, bisoprolol may be useful in hypertensives with cardiac or vascular diseases who have advanced atherosclerotic changes and sympathetic nervous system activation.

The effects of celiprolol on serum concentrations of proinflammatory cytokines in hypertensive (SHR) and normotensive (WKY) rats

BackgroundA growing body of evidence suggests that some cardiovascular drugs could modulate the level of proinflammatory cytokines. Therefore, the aim of the present study was to investigate whether celiprolol, a third generation β-adrenoceptor blocker, affects lipopolysaccharide (LPS)-induced serum concentrations of TNF-α, IL-1β, IL-6 in normotensive (WKY) and spontaneously hypertensive (SHR) rats. MethodsCeliprolol (150mgkg−1) or vehicle was administered by gavage once daily for 21 days. Arterial blood pressure was measured in conscious rats, using the tail-cuff method. Serum concentrations of proinflammatory cytokines were measured with enzyme-linked immunosorbent assay kits. Additionally, plasma concentrations of total cholesterol, HDL-cholesterol and triglycerides were evaluated. ResultsIn normotensive WKY rats celiprolol did not affect heart rate, blood pressure, or the serum concentrations of triglycerides, total cholesterol or HDL-cholesterol. In hypertensive animals the drug decreased lipid parameters, increased diastolic and mean blood pressure after the first week of administration, and produced a small but significant decrease in heart rate after the first two weeks of the treatment. In both groups of animals, celiprolol decreased LPS-stimulated serum concentration of IL-6 but did not affect levels of TNF-α and IL-1β. ConclusionsIt is suggested that the IL-6-modulating properties of celiprolol could provide additional value to the therapeutic effectiveness of the drug in the treatment of hypertension.

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial

Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome: A Prospective Randomized, Open Blinded-Endpoints Trial

Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome: A Prospective Randomized, Open Blinded-Endpoints Trial

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial

Vascular Ehlers-Danlos syndrome is a rare severe disease that causes arterial dissections and ruptures that can lead to early death. No preventive treatment has yet been validated. Our aim was to assess the ability of celiprolol, a β(1)-adrenoceptor antagonist with a β(2)-adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome. Our study was a multicentre, randomised, open trial with blinded assessment of clinical events in eight centres in France and one in Belgium. Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment. Randomisation was done from a centralised, previously established list of sealed envelopes with stratification by patients' age (≤32 years or >32 years). 33 patients were positive for mutation of collagen 3A1 (COL3A1). Celiprolol was administered twice daily and uptritrated by 100 mg steps every 6 months to a maximum of 400 mg per day. [DOSAGE ERROR CORRECTED]. The primary endpoints were arterial events (rupture or dissection, fatal or not). This study is registered with ClinicalTrials.gov, number NCT00190411. 53 patients were randomly assigned to celiprolol (25 patients) or control groups (28). Mean duration of follow-up was 47 (SD 5) months, with the trial stopped early for treatment benefit. The primary endpoints were reached by five (20%) in the celiprolol group and by 14 (50%) controls (hazard ratio [HR] 0·36; 95% CI 0·15-0·88; p=0·040). Adverse events were severe fatigue in one patient after starting 100 mg celiprolol and mild fatigue in two patients related to dose uptitration. We suggest that celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome. Whether patients with similar clinical presentations and no mutation are also protected remains to be established. French Ministry of Health, Programme Hospitalier de Recherche Clinique 2001.

Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome

Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome

Abstract 5094: Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome

Background: Vascular Ehlers-Danlos syndrome (vEDS) is a rare severe genetic disease which results from mutations in the gene encoding type III procollagen (COL3A1), characterized by vascular and/or hollow organic ruptures. No treatment is yet validated. We tested the ability of celiprolol, a beta1-adrenoceptor antagonist with a beta2-adrenoceptor agonist action, for preventing the complications of vEDS in a prospective, randomized, open, blinded endpoints trial. Methods: Fifty three previously untreated vEDS patients were randomized to a 5-year treatment with either celiprolol (n=25) or no treatment (n=28). The two groups were matched for demographic, medical historic and clinical characteristics. Celiprolol was up-titrated from 100 to 400 mg by steps of 100 mg every 6 months. The primary end-point was an arterial event (rupture or dissection, fatal or not) occurring during follow-up. Secondary endpoints were intestinal or uterine rupture or major clinical events, related to vEDS, judged by the event committee. Results: Mean duration of follow-up was 47 (±15) months. The study was ended prematurely by the safety monitoring board since significant differences were reached between two groups. The primary endpoint was reached by 5 patients (20%) in the celiprolol group and by 14 patients (50%) in the control group (hazard ratio, 0.36; 95% CI, 0.15 to 0.88; P=0.04). Primary plus secondary endpoints occurred in 6 patients (24%) in the celiprolol group and in 17 patient (61%) in the control group (hazard ratio, 0.31; 95% CI, 0.14 to 0.71; P=0.0097). Conclusions: Celiprolol effectively reduced both vascular complications and organic ruptures in vEDS patients.

Effects of celiprolol and simvastatin on the calculated risk of coronary heart disease (the Celisimva study)

Objectives. The most important risk factors for coronary heart disease are hypercholesterolemia, smoking and hypertension. To find out which one – lowering cholesterol concentration or using antihypertensive treatment-is more effective in modifying the total risk, we conducted a parallel group placebo-controlled study. The goal of the study was to assess the effect of two drugs on the calculated CHD Framingham risk score in subjects with both moderate hypertension and moderate hypercholesterolemia. Design. Celiprolol for hypertension and simvastatin for cholesterol-lowering were given as monotherapy or as combination treatment. The effects of the treatments on the CHD risk scores were calculated after 3 months. A total of 112 patients were randomized. Results. The total CHD risk decreased in simvastatin and combination groups from 26% to 19% and from 26% to 17%, respectively. Celiprolol alone decreased the risk from 25% to 21%, which was not statistically different from placebo. Conclusions. It can be concluded that subjects with moderate hypercholesterolemia and hypertension benefit more from lipid-lowering treatment with simvastatin than from blood pressure-lowering with beta blocker celiprolol.

Celiprolol increases coronary blood flow and reduces severity of myocardial ischemia via nitric oxide release.

Celiprolol is a selective beta(1)-adrenoceptor antagonist with antihypertensive actions, which causes renal vasodilation by increasing tissue nitric oxide (NO) levels. The authors tested whether celiprolol increases coronary blood flow (CBF) by increasing cardiac NO release in the ischemic heart in vivo. In open-chest dogs, coronary perfusion pressure of the left anterior descending coronary artery was reduced so that CBF decreased to 60% of control levels, and thereafter, coronary perfusion pressure was maintained constant. Ten minutes after the reduction of coronary perfusion pressure, we infused celiprolol into the left anterior descending coronary artery and measured fractional shortening and lactate extraction ratio as indices of regional myocardial contractility and metabolism. CBF significantly increased from 51.5 mL/100 g/min +/- 1.9 to 67.0 mL/100 g/min +/- 5.1 20 minutes after celiprolol infusion without changes in coronary perfusion pressure, while fractional shortening and lactate extraction ratio increased. Celiprolol also increased cardiac NO release. The L omega-nitroarginine methyl ester, the inhibitor of NO synthase, attenuated the increases in CBF, fractional shortening, lactate extraction ratio, and cardiac NO release due to celiprolol. ICI 118551, a beta(2)-adrenoceptor antagonist, did not blunt the effects of celiprolol and a nonselective beta-adrenoceptor antagonist, propranolol, increased neither CBF nor cardiac NO release, indicating that the effect of celiprolol is independent of beta-adrenoceptor blockade. It was concluded that celiprolol mediates coronary vasodilation and improves myocardial ischemia through NO-dependent mechanisms.

Long-term celiprolol therapy lowers fasting plasma leptin levels. Celiprolol Multicenter Study Group.

The effects of celiprolol on fasting plasma leptin levels, glucose tolerance, and insulin sensitivity were studied in a randomized, investigator-masked, and parallel clinical trial. Modified oral glucose tolerance tests (OGTT) were performed during the previous antihypertensive monotherapy (beta- or Ca-blocker, or ACE inhibitor), and 6 and 12 months after randomization to celiprolol (200-400 mg daily) or to control group, where the therapy was kept unchanged. One hundred sixty-nine dyslipidemic and hypertensive nondiabetics with an age range of 42-65 years and an average body mass index of 28.4 kg/m2 completed the study according to the protocol. The mean circulating leptin level decreased from 7.5 to 6.6 ng/mL in men (p < 0.05) and from 23.0 to 19.7 ng/mL in women during the 12-month celiprolol treatment. The incremental glucose area under the curve (AUC) in the 2-hour OGTT decreased from 3.8 to 3.0 h* mmol/L (p < 0.01), and insulin AUC decreased from 134 to 99 h* mU/L (p < 0.01). The insulin sensitivity index increased by 22% (p < 0.01) and the serum triglyceride level decreased by 15% in the celiprolol group. Changes in serum cholesterol were clinically insignificant. In the control group, no significant change was seen in any measured variable. A decrease in leptin levels in the celiprolol group was associated with improved insulin sensitivity, while the weight of the moderately obese patients did not change. The clinical significance of a 14% decrease in fasting plasma leptin level remains to be elucidated. The results suggest amelioration of leptin resistance during long-term celiprolol therapy.

Hemodynamic effects of celiprolol in patients with ischemic and non-ischemic cardiomyopathy

In this study, the effect of celiprolol (beta-1-antagonist with beta-2-agonistic activity) on hemodynamic and electrocardiographic parameters of patients with congestive heart failure due to ischemic (iCMP) and non-ischemic (niCMP) origin should be evaluated. Sixteen patients were included into the study, nine with iCMP, seven with niCMP. All patients were investigated by radionuclide ventriculography ( 99mTc), right heart floating catheterization, and late potential analysis and measurement of heart rate variability. All patients received 200 mg celiprolol after a 3-day period of 100 mg celiprolol/day. All patients showed, after a follow-up period of 3 months, a significant improvement of the left ventricular ejection fraction. The changes of hemodynamic parameters were more pronounced in patients with niCMP. Heart rate did not decrease in patients with niCMP. A 3-month therapy with celiprolol as an additional therapy to a preexisting heart failure therapy leads to a significant improvement of the ejection fraction in patients with congestive heart failure. Patients with niCMP seemed to profit more from this additional beta-blocking therapy.

Celiprolol, a beta-adrenoceptor antagonist with vasodilator effect, improves hemodynamic response to catecholamine, spontaneous locomotor activity, and survival in cardiomyopathic hamsters with advanced heart failure.

To assess the effects of celiprolol, which is a selective beta1-antagonist with vasodilating properties, on chronic heart failure in the cardiomyopathic hamster UM-X7.1 (CMH), we studied survival in treated CMH (celiprolol, 100 mg/kg/day) and untreated CMH. We also measured the hamsters' locomotor activity (by using an Automex system), in vivo left ventricular (LV) pressure with or without dobutamine infusion, and the myocardial beta-adrenergic-receptor density (Bmax), all at the age of approximately 210 days. Survival was significantly improved in the treated group compared with untreated group by 33.4% at the age of 210 days, and the median probabilities of survival were age 252 days in the treated group and 203 days in the untreated group (p < 0.01). The locomotor activity count was significantly higher in the treated group (14,945+/-6,895) than in the untreated group (8,264+/-2,945 counts/day; p < 0.05). The response of LV peak +/-dP/dt to dobutamine was significantly improved in the treated group by 22.9 and 34.8%, respectively, at 18 microg/kg/min. Bmax was also higher in the treated group than in the untreated group (80.1+/-15.1 vs. 65.2+/-10.6 fmol/mg; p < 0.05). This study suggests that long-term treatment with celiprolol could improve both survival and the hemodynamic responses to dobutamine, associated with the upregulation of beta-receptors, and increased locomotor activity.

Clinical Evaluation of Celiprolol in the Treatment of Atrial Tachyarrhythmias

The results of the Cardiac Arrhythmia Suppression Trial warn against the use of class Ia and Ic antiarrhythmic agents as first-line therapy for arrhythmia. The objective of the present study was to evaluate the efficacy of celiprolol, a β-blocker, in patients with supraventricular arrhythmia. Celiprolol (200 mg/day) was administered for a mean duration of 90 days (range: 32 to 128 days) to 30 patients with supraventricular arrhythmia, including 7 with chronic atrial fibrillation associated with bradycardia, 18 with paroxysmal atrial fibrillation, and 5 with premature atrial contraction (PAC). The antiarrhythmic effect of celiprolol was assessed based on changes in symptoms and heart rate determined by Holter ECG. After celiprolol therapy, arrhythmic symptoms improved in 60% of the patients. The post-treatment Holter ECG showed a decrease in the daily maximum, but not minimum, heart rate, a good control of heart rate in patients with atrial fibrillation, and a decrease of PACs. Importantly, bradycardia improved even in patients with chronic atrial fibrillation who concomitantly received digitalis. Celiprolol exerted an adequate antihypertensive effect in hypertensive patients but did not affect normal blood pressure. In conclusion, celiprolol may be used as first-line therapy for the treatment of patients with supraventricular arrhythmia.

A predictive model of the health benefits and cost effectiveness of celiprolol and atenolol in primary prevention of cardiovascular disease in hypertensive patients.

This study compares the antihypertensive and lipid modifying effects of treatment of mild to moderate hypertension with celiprolol or atenolol. It also models the 5-year cardiovascular risk reduction and the cost effectiveness of monotherapy from a partial societal perspective. The effects of celiprolol and atenolol on systolic blood pressure (SBP), total serum cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were obtained from a pooled analysis of published studies. Although celiprolol and atenolol had similar effects on SBP, celiprolol reduced the ratio of TC to HDL-C by 10.2% [95% confidence intervals (95% CI) -16.4%, -4.0%) but atenolol increased the ratio by 7.7% (95% CI of 3.4%, 12.0%). The 5-year absolute risks of an initial coronary or cerebrovascular event or cardiovascular death were computed for cohorts of patients treated with either agent or remaining untreated, using an accelerated failure time (AFT) model, based on Framingham Heart Study data. Inputs to the model were age, gender, smoking status, SBP, TC and HDL-C. The change in absolute risk was estimated using the changes in SBP and TC: HDL-C obtained from the pooled analysis. Average life-months gained by therapy were computed as differences between the Kaplan-Meier survival curves estimated from the model plus differences in 5-year cardiovascular death rates multiplied by average life expectancy obtained from life tables. Direct medical costs included drug treatment, and the costs of acute care for initial coronary and cerebrovascular events deferred by therapy over the 5-year treatment period. The model shows that in the lowest-risk base case (60-year-old men who are nondiabetic and nonsmokers with SBP of 160 mm Hg and a 5-year absolute cardiovascular risk of 12%), celiprolol (271 mg/day) is 2-fold more effective than atenolol (77.4 mg/day) in reducing coronary event risk, and equally effective in reducing cerebrovascular event risk. The number of individuals that would have to be treated for 5 years to avoid 1 coronary event is about 30 for celiprolol versus 70 for atenolol. Therapy with celiprolol yields more life-months and at current prices, the cost per life-year gained by therapy is significantly lower. Both drugs are cost effective by international standards in the treatment of patients with 5-year absolute cardiovascular risk greater than 10%, and are more cost effective in those patients at higher levels of absolute cardiovascular risk. The direct medical costs of treatment for 5 years with celiprolol are the same or slightly less than treatment with atenolol at the dosages used in the clinical trials, despite a 19% higher tablet price. Both drugs are more cost effective in patients at higher levels of absolute cardiovascular risk. These findings are sensitive to the drug dosages, tablet prices and the discount rate. Based on epidemiological and clinical data, replacing atenolol with celiprolol in patients with mild to moderate hypertension, but without overt cardiovascular disease, is predicted to have similar effects on stroke risk, but to be substantially more effective in reducing the risk of coronary events at no additional direct medical cost over a 5-year treatment period.

Celiprolol: agonist and antagonist effects at cardiac beta 1- and vascular beta 2-adrenoceptors determined under in vivo conditions in the rat.

Celiprolol is a beta-adrenoceptor antagonist which has desirable ancillary properties since it is relatively cardioselective and can exert direct vasodilator and bronchodilator effects. Here agonist and antagonist effects of celiprolol at cardiac beta 1- and vascular beta 2-adrenoceptors were determined under in vivo conditions in the rat. All experiments were carried out in catecholamine-depleted, pentobarbital anesthetized and vagotomized rats, placed under artificial respiration. I.v. administrations were made via the femoral vein. Blood pressure was measured from the cannulated right carotid artery and heart rate was recorded with a cardiotachometer. Celiprolol (10 micrograms/kg to 1 mg/kg i.v.) produced dose-related increases in heart rate and decreases in mean carotid artery blood pressure which were of longer duration than those mediated by standard agonists of beta 1-(isoprenaline) or beta 2-(salbutamol) adrenoceptors respectively. Although the maximal increase in heart rate by celiprolol (110 +/- 4 beats/min, n = 7) was approximately half that of isoprenaline (198 +/- 1 beats/min, n = 5), isoprenaline acted at doses 200-fold lower than celiprolol. Betaxolol (0.03-0.3 mg/kg i.v.), a beta 1-adrenoceptor antagonist, inhibited strongly and with similar potency the tachycardiac effects of celiprolol (DR10 = 45 micrograms/kg i.v.) as well as isoprenaline (DR10 = 45 micrograms/kg i.v.). On the other hand, the hypotensive effects of celiprolol and salbutamol were antagonized markedly and with similar potency by ICI 118,551, a relatively selective beta 2-adrenoceptor antagonist (DR10 = 15 and 25 micrograms/kg i.v. respectively). In rats pretreated with celiprolol (0.03 to 0.3 mg/kg i.v.), the heart rate dose-response curves to isoprenaline were shifted to the right of those determined in matched groups of vehicle-pretreated animals. In this respect, celiprolol was half as potent as betaxolol in blocking cardiac beta 1-adrenoceptors. Furthermore, celiprolol also antagonized the hypotensive effects of salbutamol, but, in this respect, celiprolol was 90-fold less potent than ICI 118,551. In conclusion, these results clearly indicate that celiprolol has the ability of stimulating and blocking not only cardiac beta 1- but also vascular beta 2-adrenoceptors. The effects on cardiac beta 1-adrenoceptors as well as the agonism of beta 2-adrenoceptors are produced by similar doses of celiprolol. These doses are notably lower than those necessary to block beta 2-adrenoceptors. Thus, this pharmacological profile, which has also been demonstrated in humans, indicates that celiprolol is a modulator of cardiac beta 1-adrenoceptors with vascular beta 2-adrenoceptor agonist properties.

Evaluation of glucose tolerance during treatment with celiprolol in patients with Mild Arterial Hypertension without diabetes mellitus

SummaryA prospective evaluation of the metabolic effects of Celiprolol, a third generation Beta-Blocking agent was done by 10 general practitioners in 45 mildly hypertensive patients, (diastolic blood pressure > 95 mm/Hg and < 115 mm/Hg.In 43 patients with complete data, blood pressure and resting heart rate decreased significantly after treatment, but weight and metabolic parameters were unchanged. After 6 months therapy the 22 patients with an impaired glucose tolerance test (IGTT) had a significant decrease in plasma glucose and insulin values, and a tendency for increased HDL. These favorable metabolic effects of Celiprolol in mildly hypertensive patients with an abnormal GTT are different from the findings with other beta-blockers and justify further study.

Effect of celiprolol therapy on arterial dilatation in experimental hypertension.

1. It has recently been suggested that therapy with beta-adrenoceptor blockers reduces peripheral arterial resistance via enhanced vascular dilatation. Therefore, we studied the effects of celiprolol, which is a specific beta 1-antagonist that has a weak beta 2-agonist action, on arterial tone in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. 2. Two doses of celiprolol (5 and 50 mg kg-1 day-1) were administered to the SHR, while the WKY rats received only the higher dose of the drug. During the 12-week treatment period the higher dose attenuated the increase in blood pressure by approximately 20 mmHg in SHR, whereas the lower dose was without significant antihypertensive effect. Celiprolol therapy did not affect blood pressure in the normotensive WKY rats. 3. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Interestingly, endothelium-mediated relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) in the absence and presence of the cyclo-oxygenase inhibitor, diclofenac, were equally enhanced in both celiprolol-treated SHR groups. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) practically abolished the relaxations to ACh in all SHR irrespective of whether they had received celiprolol, whereas in WKY rats L-NAME only attenuated the responses to ACh. However, no differences were found between the SHR groups in relaxations to ACh when hyperpolarization of smooth muscle was prevented by precontractions induced by 50 mM KCl. Vasorelaxation of NA-precontracted rings to the exogenous nitric oxide donor, nitroprusside, was also moderately augmented in both celiprolol-treated SHR groups, while the relaxation to beta-adrenoceptor agonist, isoprenaline, remained equally impaired in all SHR whether or not they had received celiprolol. No differences were observed between the two WKY groups in the responses to ACh, nitroprusside or isoprenaline. 4. Contractile sensitivity of mesenteric arterial rings to the receptor-mediated agonists, NA and 5-hydroxytryptamine, was comparable in all study groups. 5. In conclusion, SHR treatment with either the low or the higher dose of celiprolol was accompanied by enhancement of both endothelium-dependent and endothelium-independent nitric oxide-mediated arterial relaxation, possibly via a hyperpolarization mechanism. Interestingly, this effect appeared to be independent of the reduction in blood pressure.

Mechanism of vasodilating action of nebivolol

A decrease in endothelium-derived relaxing factor or nitric oxide has been proposed as a potential mechanism of increased vascular resistance in hypertension. An increase in the generation of superoxide anions, which degrade nitric oxide and induce platelet aggregation, may also compromise regional blood flow in hypertension. Recent studies show that human neutrophils generate nitric oxide, which has a similar biologic profile to the endothelium-derived relaxing factor. This study measured nitric oxide synthase activity and superoxide generation in human neutrophils and platelet aggregation in patients with essential hypertension. Nitric oxide synthase activity, measured as conversion of 3H-L-arginine to 3H-L-citrulline, in peripheral blood neutrophils was decreased in hypertensive subjects (percent conversion of 3H-L-arginine: 4.2 ± 0.5 vs 9.0 ± 3.0 in control subjects; p < 0.01). Neirtrophil superoxide anion generation, measured as conversion of ferricytochrome C to ferrocytochrome C, in response to phorbol-12-myristate 13-acetate (100 ng/ml) was higher in hypertensive subjects (17.5 ± 8.1 vs 13.2 ± 3.0 nmoles/106 cells/10 minutes in control subjects; p < 0.05). Patients were treated with a selective β blocker, celiprolol, for 8 weeks. Supine blood pressure decreased from 177/103 mm Hg (mean ± SD 18/7) to 160/92 mm Hg (mean ± 10/5; p < 0.02), while heart rate was unchanged (73 ± 11 vs 69 ± 10 beats/min). Epinephrine and adenosine diphosphate-induced platelet aggregation was also increased in hypertensive subjects. Nitric oxide synthase activity increased after therapy with celiprolol (4.2 ± 0.5 to 8.9 ± 0.4%; p < 0.01), and superoxide anion generation decreased (17.5 ± 8.1 to 3.0 ± 1.0 nmoles/106 cells/10 minutes; p < 0.01). Platelet aggregation also decreased during celiprolol therapy. The increase in superoxide radical generation, decrease in nitric oxide synthase activity, and increased platelet aggregation may relate to the pathophysiology of hypertension. The novel effects of celiprolol described in this study may be the basis of cardioprotective effects of β blockers.

Effects of celiprolol and metoprolol on diabetic angiopathy in a type I diabetes mellitus rat model

Effects of celiprolol and metoprolol on diabetic angiopathy in a type I diabetes mellitus rat model