Acute effects of alpha- and beta-adrenoceptor blockade on plasma atrial natriuretic peptides during exercise in elderly patients with mild hypertension.

In a randomized study in 26 elderly patients with mild essential hypertension, acute effects of alpha- and beta-adrenoceptor blockade on plasma ANP levels were examined at rest and during ergometric exercise. Plasma ANP level and LVEF were measured before and after administration of prazosin (an alpha 1-adrenergic blocker), atenolol (a cardioselective beta-adrenergic blocker), or carteolol (a nonselective beta-adrenergic blocker). Plasma ANP level was increased by exercise. Carteolol and atenolol increased plasma ANP levels at rest and during exercise, but the effect of atenolol was not statistically significant. Prazosin significantly suppressed the ANP values at rest and during exercise. The LVEF was increased by prazosin and decreased by beta-blockers, especially by carteolol. Multivariate regression analysis showed that LVEF was the most significant predictor of the plasma ANP level at maximal exercise; the resting blood pressure and heart rate were not predictors of this value. The results showed that single administrations of an alpha-blocker and a nonselective beta-blocker had opposite effects on the plasma ANP level both at rest and during exercise in elderly patients with mild essential hypertension. The observed difference in the ANP response seems to be related to changes in left ventricular function rather than changes in blood pressure or heart rate.     

The Effect of Acebutolol on Plasma Lipids,Blood Glucose and Serum Insulin Levels

Abstract The effect on plasma lipids of acebutolol given orally over a 6-month period to 18 patients with essential hypertension was studied. There were no significant changes in the concentrations of plasma total cholesterol, LDL cholesterol, VLDL cholesterol and triglycerides during treatment. The level of HDL cholesterol decreased slightly but not significantly during treatment. Plasma free fatty acids decreased significantly (p<0.05) during treatment with acebutolol. During an oral glucose tolerance test, blood glucose values were elevated after acebutolol therapy at 60 (p<0.05) and 120 min (p<0.05). No impairment of insulin release was observed after acebutolol therapy.     

Increased Plasma Free Dopamine after Treatment with Atenolol and Oxprenolol in Essential Hypertension

ABSTRACT. In 19 men aged 50 with essential hypertension, 18 weeks' treatment with atenolol (n=9) or oxprenolol (n=10) increased supine plasma free dopamine concentrations by 78% (p<0.05) and 121 % (p<0.001) respectively. Increments in plasma dopamine were observed in all patients except for one treated with atenolol. Supine peripheral venous adrenaline and noradrenaline concentrations were not influenced by β-blockade. The mechanism and significance of the present elevation of plasma free dopamine by β-blockade are unknown. However, increased plasma free dopamine may be involved in the hypotensive effect of chronic β-adrenergic blockade, both β-1 selective and non-selective, and may lend further support to decreased dopaminergic activity in essential hypertenison.     

Effects of ramipril on the neurohormonal response to exercise in patients with mild or moderate congestive heart failure

Static measurements of plasma neurohormones at rest may notbe adequate to detect alterations in cardiovascular controlmechanisms in congestive heart failure (CHF). Therefore, itis of interest to study neurohormonal activation during differentphysiological conditions. Plasnw neurohormones were measuredin 54 patients on diuretic therapy for mild or moderate CHF.Samples were taken at rest and immediately after maximal bicycleexercise, before and after 12 weeks of treatment with ramiprilor placebo. There was a strong correlation between the plasmalevels of each hormone before and after exercise. An inversecorrelation existed at baseline between exercise duration andangiotensin II levels after maximal exercise (r= – 0·30,P=0·03), but not at rest. Plasma levels of angiotensinII, aldosterone, atrial natriuretic peptide (ANP) and noradrenalinewere increased after maximal exercise compared to rest. Plasmaangiotensin converting enzyme activity and ANP were reducedby ramipril compared to placebo, both at rest and after exercise,but levels of angiotensin II, aldosterone and nordrenaline werenot significantly affected Thus, exercise consistently activatesneurohormonal systems in patients with CHF. Patients with thelowest exercise duration had the highest angiotensin II levelsafter exercise. Measurements of plasma neurohormones after maximalexercise provide limited additional value to measurements atrest.     

Natriuretic peptide response to dynamic exercise in patients with atrial fibrillation

BACKGROUND: In patients with atrial fibrillation (AF) information regarding exercise release of atrial natriuretic peptide (ANP) is sparse and data on plasma brain natriuretic peptide (BNP) response to exercise is lacking. The aim of this study was to investigate plasma ANP and BNP response to exercise in patients with permanent AF and to assess if the response was different from the response in healthy age- and sex-matched control subjects. METHODS: Plasma venous concentrations of ANP and BNP were determined at rest, at peak exercise and 30 min from the end of exercise in 38 patients with permanent AF and in 43 age- and sex-matched healthy control subjects. RESULTS: Plasma concentrations of ANP and BNP were significantly higher in AF patients compared with the healthy control group at rest, peak exercise and after 30 min of recovery (p<0.0001). ANP and BNP increased significantly during exercise in both patients with AF and in the healthy control subjects (p<0.05). The increase in plasma concentration of ANP and BNP during exercise was significantly higher in AF patients compared with healthy controls (p=0.0002 for ANP; p<0.0001 for BNP). In the recovery period plasma BNP decreased significantly (p<0.0001) where as the decrease in plasma ANP was insignificant (p=0.4). CONCLUSIONS: Patients with permanent AF have elevated levels of ANP and BNP at rest and exhibit much higher exercise release compared to healthy control subjects. This enhanced secretion of potent vasodilating and natriuretic agents may represent an important compensatory mechanism to improve exercise capacity in patients with AF.     

Plasma concentrations of atrial natriuretic peptide during physical exercise in patients with congestive heart failure

Summary Plasma concentrations of atrial natriuretic peptide (ANP) were measured in 25 patients with organic heart disease during physical exercise (baseline and maximum workload) in order to investigate if the responsiveness of stimulated release of ANP is still preserved in patients with heart failure and chronically elevated cardiac filling pressures. Since plasma concentrations of ANP are known to be positively correlated with mean right atrial pressures (RAP), the patients were divided into two groups according to their resting RAP: group I: those with normal RAP ( 5 mmHg; n=11); group II: those with elevated RAP (>5 mmHg; n=14). Under baseline conditions RAP (3.2±0.4 mmHg vs. 8.8±0.7 mmHg; p<0.01), pulmonary artery diastolic pressure (PADP; 9.5±0.9 mmHg vs. 17.9±1.8 pg/ml; p.<0.01), and plasma ANP levels (128±19 pg/ml vs. 204±60 pg/ml; p<0.06) were significantly lower in group I than in group II. Both at rest and during maximum workload, plasma ANP concentrations were closely related to RAP, PADP, and mean pulmonary artery pressures in both groups.During exercise in all patients, RAP and PADP significantly increased, as well as plasma ANP concentrations. Similar increments in plasma ANP concentrations were accompanied by greater changes in RAP in group II than in group I. However, identical changes in PADP lead to identical increments in plasma ANP concentrations in both groups.In conclusion, the increments of plasma ANP concentrations during physical exercise were independent of the resting values of PADP, RAP, and plasma ANP concentrations. During exercise the increments in plasma ANP concentrations for identical changes of PADP were not significantly influenced by the resting conditions; only in patients with elevated RAP at rest did increments in RAP during exercise induce a slightly reduced ANP release compared with patients who had normal right ventricular filling pressures. These data indicate that the responsiveness of ANP release during physical exercise is only slightly impaired in patients with heart failure and chronically elevated cardiac filling pressures.Dedicated to Professor Dr. F. Loogen on the occasion of his 70th birthday.     

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

Neither physical exercise nor α1- and β-adrenergic blockade affect plasma endothelin concentrations

Endothelins (ET) are recently discovered vasoconstrictor agents released from endothelial cells and have been the object of intense investigation by researchers. Many of the factors that seem to influence the release of ET are modified by prolonged exercise. The purpose of this study was to investigate the effect of physical exercise on ET plasma concentrations and the effect of α- and β-blockade on ET concentrations at rest and during exercise. Fifteen young volunteers (age 20–35 years) performed an exercise test on a bicycle ergometer. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate was achieved; after a 2 min recovery period at 50 W the test continued for 15 min at 60% maximal work load. Blood samples were taken for ET determination before and after the test. After 1 week, the test was repeated. In the 2 days before either the first or the second test, each volunteer randomly received carvedilol (C) (25 mg), an α₁-adrenoceptor and β-adrenoceptor blocker. There was no significant difference in ET concentrations after exercise with or without C administration (1.24 ± 0.66, 1.42 ± 0.83, 1.66 ± 1.15, 1.61 ± 0.87 pg/mL), showing that prolonged aerobic exercise does not affect plasma ET levels. Moreover, in our healthy young volunteers, blockade of α- and β-adrenoceptors had no effect on ET levels at rest and after exercise.     

Plasma ANP and cyclic GMP after physical exercise in patients with mitral valve disease and in healthy subjects

Plasma levels of both atrial natriuretic peptide (ANP) and cyclic GMP are elevated in patients with various heart diseases as compared to healthy subjects. In this study patients with advanced mitral valve disease (Group A) and healthy subjects (Group B) were exposed to symptom-limited upright stepwise physical exercise on a cycle ergometer. Concentrations of ANP and cyclic GMP were measured in plasma at rest (20 min in supine position) or 5 min after physical exercise by specific radioimmunoassays. Here we show that short dynamic exercise caused a significant increase in plasma levels of ANP and cyclic GMP, in both groups. In Group A strong correlation between plasma ANP and cyclic GMP was found at rest (r = 0.91, P < 0.001, n = 11) and after physical exercise (r = 0.85, P < 0.001, n = 11). In contrast, there was no correlation between plasma concentrations of ANP and cyclic GMP in Group B at rest (r = −0.16, P > 0.05, n = 10) or after exercise loading (r = 0.14, P > 0.05, n = 10). Absolute increases in circulating levels of both substances were not found to correlate in either group. These data suggest that exercise-induced elevations in plasma cyclic GMP may be due not only to ANP release but also to an as yet undetermined factor, possibly EDRF/NO.     

Response of plasma norepinephrine and epinephrine to dynamic exercise in patients with congestive heart failure

The activity of the sympathetic nervous system is increased at rest in patients with congestive heart failure. To determine whether this augmentation is carried over during dynamic upright exercise, 14 patients with congestive heart failure were stressed maximally during upright bicycle ergometry. Plasma norepinephrine and epinephrine levels were measured in the basal upright (sitting) posture before and during maximal exercise. The results were compared with those in six healthy control subjects before and during maximal exercise. Plasma norepinephrine increased during exercise from a mean (± standard error of the mean) of 650 ± 95 to 1,721 ± pg/ml in the group with heart failure. This increase was significantly less (p < 0.001) than that in the control group (from 318 ± 36 to 3,230 ± 418 pg/ml). However, for equivalent levels of total body oxygen consumption (V?O₂), the group with heart failure had higher levels of plasma norepinephrine than the control group. Plasma epinephrine was similar in the two groups in the basal upright position (92 ±18 and 92 ± 26 pg/ml), but it increased more during exercise in the normal subjects (743 ± 210 pg/ml) than in the group with heart failure (167 ± 67 pg/ml) (p < 0.001). The percent increase in norepinephrine correlated with the percent change in V?O₂ in the group with heart failure (r = 0.62, p < 0.02), but the percent change in epinephrine did not.There is, therefore, a disturbance in the sympathetic nervous system during exercise in patients with congestive heart failure. Although norepinephrine increases in such patients to a greater extent than in normal subjects at lower levels of exercise, the extremely high levels of norepinephrine and epinephrine generated by normal subjects during maximal upright exercise do not occur in patients with heart failure.     

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

Aims/hypothesis In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients.Materials and methods We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-¹³C]palmitate and [6,6 -²H₂]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type.Results Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05).Conclusions/interpretation This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.     

Role of atrial natriuretic peptide in hemoconcentration during exercise

Changes in plasma levels of atrial natriuretic peptide (ANP) and albumin, and blood hematocrit (Hct) during treadmill exercise were studied in 6 healthy men before and after beta-adrenergic blockade. Plasma ANP levels increased during exercise and then gradually decreased. There was a concomitant increase in both Hct and plasma albumin concentrations. Prior administration of a long-acting propranolol, 160 mg daily for 3 consecutive days, markedly elevated plasma ANP levels before, during and after exercise. In addition, the mean basal Hct increased significantly and further rose during exercise after propranolol administration. When increments in plasma ANP concentrations during exercise in individual subjects were compared with those in Hct, there was a significant positive correlation between the two variables before and after propranolol administration. The results indicate a close relationship between the changes in plasma ANP and those in Hct during exercise at different ANP levels, and suggest that ANP may be at least one of the factors involved in the hemoconcentration associated with exercise.     

Augmented response in plasma brain natriuretic peptide to dynamic exercise in patients with left ventricular dysfunction and congestive heart failure

OBJECTIVES: We have previously demonstrated that patients with symptomatic congestive heart failure (CHF), but not with asymptomatic left ventricular dysfunction (LVD), have augmented plasma atrial natriuretic peptide (ANP) response to exercise. Plasma brain natriuretic peptide (BNP) response to exercise is less extensively studied. The aim of this study was to determine whether responses of plasma BNP during exercise normalized for exercise workload are altered in patients with LVD and CHF. SUBJECTS AND METHODS: Twenty-nine patients with LVD, 32 patients with CHF (NYHA classes II-III) and 27 age-matched control subjects were studied. Ventilatory, plasma ANP and BNP responses were assessed during symptom-limited cardiopulmonary exercise testing. Plasma natriuretic peptide levels were measured at rest and immediately after peak exercise. The increment in plasma BNP was divided by the increment in oxygen uptake (VO2) from rest to peak exercise, and this ratio [BNP exercise ratio: (peak BNP - rest BNP)/(peak VO2 - rest VO2)] was compared amongst the three groups. RESULTS: Peak VO2 (Control, LVD and CHF: 28.2 +/- 1.7, 21.1 +/- 1.8, 16.2 +/- 0.6 ml, min(-1) kg(-1), respectively), anaerobic threshold and peak workload became smaller as heart failure worsened. Resting and peak plasma ANP levels were significantly higher only in CHF, whilst resting and peak plasma BNP levels displayed a significant and continuous increase from normal subjects to LVD and CHF. The ANP exercise ratio (1.25 +/- 0.36, 2.61 +/- 0.57, 7.72 +/- 1.65, ANOVA P = 0.0002) was significantly higher only in patients with CHF, whilst the BNP exercise ratio (0.35 +/- 0.10, 2.60 +/- 0.69, 4.98 +/- 0.97, ANOVA P = 0.0001) was significantly higher in patients with LVD and became progressively higher in patients with CHF. CONCLUSIONS: These data showed that the BNP exercise ratio, an exercise plasma BNP response normalized with exercise workload, was augmented in patients with LVD, and became progressively higher in CHF, suggesting that an augmented exercise BNP ratio exists early in the course of developing CHF.     

Hemodynamic Effects at Rest and during Exercise in Long-term Treatment with Prazosin in Chronic Congestive Heart Failure

ABSTRACT. The long-term effects of prazosin in chronic congestive heart failure were studied in 10 patients (New York Heart Association class III-IV) in a double-blind cross-over study. Patients with systolic blood pressure > 120 mmHg and left ventricular filling pressure > 15 mmHg were included. Prazosin lowered the arteriovenous oxygen difference both at rest and during exercise (p < 0.05), increased cardiac index (p < 0.01) and reduced right atrial pressure and systemic vascular resistance (p < 0.05) during exercise. Left ventricular filling pressure was also reduced, but not significantly, during exercise. Our data show that prazosin has beneficial long-term effects during exercise in patients with chronic congestive heart failure.     

Effect of exercise on circulating atrial natriuretic peptide and left ventricular ejection fraction in healthy persons and patients with coronary artery disease

Radionuclide angiographic measurements of left ventricular ejection fraction were performed at rest and during exercise in 10 normal persons and 11 patients with coronary artery disease. Exercise was continued on a supine bicycle exercise table up to a symptom-limited maximum. Plasma levels of atrial natriuretic peptide (ANP) were also determined at rest and during exercise. Ejection fraction in the normal volunteers was 59 +/- 3% (mean +/- SEM) at rest and increased significantly (p less than 0.01) to 69 +/- 3% during exercise. Ejection fraction in the patients was 47 +/- 5% at rest and did not change significantly during exercise (51 +/- 7%). Plasma ANP in the normals rose significantly (p less than 0.01) from 62 +/- 16 pg/ml at rest to 454 +/- 94 pg/ml during exercise. Plasma ANP in the patients also rose significantly (p less than 0.01) from 231 +/- 102 pg/ml to 794 +/- 170 pg/ml. The response of plasma ANP to exercise was enhanced significantly (p less than 0.05) in the patients as compared with the normals in relation to ejection fraction by analysis of covariance. In both the normals and the patients, plasma ANP was inversely and significantly correlated with ejection fraction during exercise (r = -0.46, p less than 0.05, n = 21), however, not at rest. Because it has been reported that plasma ANP is correlated positively with pulmonary artery wedge pressure, the estimation of plasma ANP during an exercise stress test might be used for the evaluation of cardiac reserve in coronary artery disease.     

Relationships Between Biomarkers and Left Ventricular Filling Pressures at Rest and During Exercise in Patients After Myocardial Infarction

BackgroundIncreased pulmonary capillary wedge pressure (PCWP) is an independent prognostic predictor after myocardial infarction (MI), but PCWP is difficult to assess noninvasively in subjects with preserved ejection fraction (EF). We hypothesized that biomarkers would provide information regarding PCWP at rest and during exercise in subjects with preserved EF after MI.Methods and ResultsSeventy-four subjects with EF >45% and recent MI underwent right heart catheterization at rest and during a symptom-limited semisupine cycle exercise test with simultaneous echocardiography. Plasma samples were collected at rest for assessment of midregional pro–A-type natriuretic peptide (MR-proANP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), copeptin, and midregional pro-adrenomedullin (MR-proADM). Plasma levels of MR-proANP and PCWP were associated at rest (r = 0.33; P = .002) and peak exercise (r = 0.35; P = .002) as well as with changes in PCWP (r = 0.26; P = .03). Plasma levels of NT-proBNP and PCWP were weakly associated at rest (r = 0.23; P = .03) and peak exercise (r = 0.28; P = .02) but not with changes in PCWP (r = 0.20; P = .09). In a multivariable analysis, plasma levels of MR-proANP remained associated with rest and exercise PCWP (P < .01), whereas NT-proBNP did not. Plasma levels of Gal-3, copeptin, and MR-proADM were not associated with PCWP at rest or peak exercise.ConclusionsIn subjects recovering from an acute MI with preserved EF, plasma levels of natriuretic peptides, particularly MR-proANP, are associated with filling pressures at rest and during exercise.     

Effects of β1-Adrenoceptor Blockade in the Treatment of Hypertension during Pregnancy in Diabetic Women

ABSTRACT The effects of β₁-blockade were investigated in 18 hypertensive pregnant diabetic women. The same women served as controls, covering a period just before therapy. The blood pressure was reduced in 14 women (p<0.01). The change in blood glucose homeostasis was statistically not different from the control period. Insulin doses were not affected. The fetal heart rate was affected by therapy, causing a decrease in baseline rate (p<0.05) and in acceleration amplitude (p<0.05). Although the incidence of suspect fetal distress, intrauterine growth retardation and preterm delivery was high, all surviving infants had normal Apgar scores at 5 and 10 min. Perinatal mortality consisted of one stillbirth. Except for respiratory problems, the incidence of neonatal complications was low. All survivors were healthy at follow-up. We found β₁-blockade to be effective and safe in this group of high-risk pregnancies, and suggest it as an alternative for anti-hypertensive therapy in diabetic pregnancy.     

Effects of chronic β-blockade on rest and exercise hemodynamics in mitral stenosi

β-blocker therapy for mitral stenosis is controversial. This study compares right and left heart hemodynamics at rest and supine submaximal exercise in patients (n = 7) receiving chronic β-antagonists with untreated patients (n = 17) matched for age (mean ± SD = 51 ± 12 years) and valve area (0.7 ± 0.2 cm²/m²). Little benefit was observed with treatment at rest. Although pulmonary capillary wedge pressures (PCWP) were lower during exercise in the β-blocker group (22±4 vs. 31 ± 9 mmHg; P>0.05), exercise performance was not enhanced and cardiac output response during exercise was reduced (control = 41% increase vs. 12% for β-blockade). PCWP rose rapidly when diastolic filling periods were >300 msec in both groups. Pulmonary capillary wedge pressure was found to be a nonlinear functions (P<0.001) of diastolic filling period (PCWP = 15.9 + 5.84 × 10⁵/dfp²). These data suggest that there is a critical heart rate in patients with mitral stenosis above which hemodynamic compromise rapidly occurs. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Melatonin Secretion Related to Side-effects of β-Blockers from the Central Nervous System

ABSTRACT In two studies of hypertensive patients the relationship between β-blocker-induced CNS side-effects and the nightly urinary secretion of melatonin was analysed. In one group (n=10) placebo, atenolol (mean dose 86 mg/day) or propranolol (mean dose 305 mg/day) were given in a double-blind, randomised design. In the other (n = 13) 100–400 mg metoprolol was given daily (mean dose 197 mg). After 4 weeks of treatment all β-blockers reduced melatonin excretion, but the effect was significant only for metoprolol. Sleep disturbance records revealed more disturbed nights in the metoprolol group compared with the propranolol and the atenolol groups, even when the difference in age between the groups was controlled for. In the metoprolol group a significant relationship (p<0.05) was found between the fall in melatonin and the percentage of disturbed nights. Severe CNS side-effects, such as nightmares, occurred only in patients treated with metoprolol (21%), which in all cases were accompanied by low levels of melatonin. Our data suggest that the CNS side-effects during β-blockade are related to a reduction of melatonin levels.     

Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension

OBJECTIVE: The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH). DESIGN AND METHODS: Eighteen physically active patients with moderate EH were included: age: 46.9 +/- 2.38 years, weight: 83.9 +/- 2.81 kg, blood pressure (BP): 155.8 +/- 3.90/102.5 +/- 1.86 mm Hg, heart rate: 73.6 +/- 2.98 min(-1). After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day. RESULTS: Nebivolol treatment resulted in a significant (P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO(2)) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged. CONCLUSIONS: Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.