Chronic Beta-adrenergic Blockade Research Articles

Beta-adrenergic blockade increases GLUT4 and improves glycemic control in insulin-treated diabetic Wistar rats.

Unequivocal modulation of glycemic homeostasis by chronic beta-adrenergic blockade in diabetes has never been demonstrated. This study investigates the participation of beta-adrenergic system in glycemic control and muscle glucose transporter GLUT4 expression in insulin-treated diabetic rats. Insulin-treated diabetic Wistar (W) or spontaneously hypertensive rats (SHR) were additionally treated with propranolol, and glycemic homeostasis and expression of some target mRNAs and proteins in soleus and extensor digitorum longus (EDL) muscles were analyzed. Insulin improved glycemic control in both strains. Importantly, in W, propranolol promoted a further improvement in glycemic control, which was accompanied by decreased PKA and Tnf expression, and increased Slc2a4 and GLUT4 in EDL. Those effects were not observed in diabetic-SHR. Propranolol-induced decrease in beta-adrenergic activity in skeletal muscles of insulin-treated diabetic Wistar rats increases GLUT4 expression in EDL, improving glycemic control. These outcomes represent a positive effect of nonselective beta-blockade, which might be extended to autonomic neuropathy.

Chronic beta-adrenergic blockade prevents volume overload-induced re-localization and oxidation of soluble guanylyl cyclase

Chronic beta-adrenergic blockade prevents volume overload-induced re-localization and oxidation of soluble guanylyl cyclase

Abstract 373: A Novel Haplotype In The G(alpha)s Gene Alters Gene Expression And Responsiveness To Receptor Stimulation And Predicts Cardiac Performance In Humans

Background: Transgenic mice with cardiac Gαs overexpression exhibit enhanced inotropic and chronotropic responses to sympathetic stimulation, but develop cardiomyopathy with age. In contrast, chronic beta-adrenergic receptor blockade (beta-AR) mitigates cardiac dilation and depressed left ventricular function in these models. We tested the hypothesis that naturally occurring variants in regulatory regions of the human gene GNAS encoding Gαs result in altered Gαs expression and signal transduction properties in humans. Methods and results: Sequencing the promoter and intron 1 of GNAS revealed 11 single nucleotide polymorphisms resulting in three common haplotypes. In reporter assays haplotype *3 constructs exhibited significantly higher promoter activity compared to haplotype *1 and *2 constructs. In hearts from 54 patients under chronic beta-AR blockade scheduled for coronary artery bypass grafting (CABG) Gαs mRNA expression was more than 50% higher in homozygous *3 carriers (*3/*3) than in heterozygous (*3/−) and negative *3 (−/−) carriers (Gαs/Actin, 0.16±0.06 vs. 0.10±0.03 vs. 0.09±0.04; p=0.002). Consistent with increased Gαs expression, functional studies showed that *3/*3 carriers had higher basal activities of adenylyl cyclase (AC, 32.4±12.9 vs. 29.1±7.9 vs. 25.5±5.3 pmol/min/mg; p=0.019) and maximal isoproterenol-stimulated activities were markedly higher for the *3/*3 compared to *3/− and −/− carriers (79.3±29.7 vs. 66.7±16.2 vs. 57.3±11.1 pmol/min/mg; p=0.002). Direct AC stimulation with Forskolin was unaffected by GNAS haplotypes. Hemodynamic measurements in 137 bypass patients under chronic beta-AR blockade revealed a higher cardiac index (2.2±0.2 vs. 1.9±0.1 vs. 1.8±0.1 l min-1 m-2; p=0.025) in *3/*3 carriers. This was also in line with a lower NYHA functional class (1.8±0.2 vs. 2.2±0.1 vs. 2.3±0.1; p=0.040) and NT-proBNP levels (339±87 vs. 746±110 vs. 1365±259 pg/ml; p=0.002). Summary: Increased Gαs expression due to a functional haplotype results in altered signal transduction properties and may have salutary effects on cardiac performance in CABG patients under chronic beta-AR blockade. Our data therefore could help to translate results from transgenic mice to genotype-phenotype correlations in humans.

Vascular endothelial effects of chronic beta-adrenergic receptor blockade in heart failure

Vascular endothelial effects of chronic beta-adrenergic receptor blockade in heart failure

β-Blocker Effects on Respiratory Sinus Arrhythmia and Baroreflex Gain in Normal Subjects

The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. Twenty normal subjects (28+/-2 years old) were randomized to receive a hydrophilic (nadolol) beta-blocker, a lipophilic (metoprolol) beta-blocker, and placebo. After 1 week of therapy, a spectral analysis was made of the variability in heart rate and systolic BP during controlled breathing at 16 breaths/min. The high-frequency component was calculated for the RR interval (measure of RSA) and systolic pressure, and the squared coherence and phase functions were assessed between RR and systolic pressure fluctuations in the respiratory band; a negative phase means that RR changes follow systolic pressure changes. The gain in the relationship between the two signal fluctuations was also calculated. Both beta-blockers increased the mean (+/-SD) RR interval (placebo=808+/-21, nadolol=1,054+/-30, metoprolol=1,031+/-27 ms; p<0.0001), RSA (placebo=542, nadolol=1,177, metoprolol=1,316 ms2; p=0.002), and the gain (placebo=13.6+/-1.5, nadolol=21.9+/-2.8, metoprolol=24.5+/-3.6 ms/mm Hg; p<0.002), and both modified the phase function (placebo=-21.1+/-5.3, nadolol=-1.8+/-4.9, metoprolol=-2.9+/-4.2 degree; p<0.0001). No difference was found between nadolol and metoprolol. Chronic beta-adrenergic blockade enhanced both RSA and baroreflex gain and reduced the phase between the RR interval and systolic pressure oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.

What Can We Learn from Provoking Ischemia?

What Can We Learn from Provoking Ischemia?

Direct Effects of chronic beta-adrenergic receptor blockade on left ventricular and myocyte function in a model of tachycardia-induced congestive heart failure

Background: Chronic beta-receptor blockade (beta-blockade) has been reported to improvesymptoms and increase survival in patients with congestive heart failure (CHF); however, whether the mechanisms for the effects of beta-blockade in CHF are due to modulating chronotropy, inotropy, or both remains unknown. To address this issue, left ventricular function and isolated myocyte function were examined with chronic beta-blockade in a rapid pacing model of CHF, thereby eliminating potential chronotropic effects of beta-blockade. Methods and Results: Pigs were randomly assigned to three groups of six pigs each: supraventriculartachycardia (SVT): 3 weeks of atrial pacing at 240 beats/min; SVT/beta-blockade: 3 weeks of rapid pacing and beta-blockade (25 mg atenolol twice daily on days 14–21 of pacing); control group, sham control animals. This dosage schedule for beta-blockade was chosen because catecholamines are persistently elevated by day 14 in this model of CHF. Left ventricular fractional shortening and end-diastolic dimension were measured by echocardiography in the conscious state with a resting ambient heart rate. Isolated left ventricular myocyte function was examined using high-speed videomicroscopy. Supraventricular tachycardia caused left ventricular dilation (5.4 ± 0.1 vs 3.5 ± 0.1 cm) and reduced fractional shortening (12 ± 1% vs 35 ± 1%) compared with control animals (P < .05). The SVT/beta-blockade group showed no significant effects on left ventricular size or function compared with the SVT group, but their ambient resting heart rate was reduced by 20% relative to the SVT group (P < .05). Myocyte shortening was reduced in the SVT group (2.2 ± 0.1% vs 4.5 ± 0.1%, P < .05) compared with the control group and increased from SVT only values with beta-blockade (2.7 ± 0.1%, P < .05). Similarly, myocyte shortening velocity was similarly reduced in the SVT and SVT/beta-blockade groups (31 ± 1 and 32 ± 1 μm/s) compared with the control group (51 ± 1 μm/s, P < .05). With SVT/beta-blockade myocyte contraction duration was prolonged (525 ± 5 ms) compared with SVT-only or control values (469 ± 9 and 473 ± 4 ms, P < .05). Thus, institution of beta-1-selective blockade during the development of SVT-induced CHF altered the temporal characteristics of the myocyte contraction process, which resulted in improved myocyte shortening. Conclusions: In a model of CHF due to the maintenance of a chronically elevated heart rate,institution of beta- 1-selective blockade during the progression of the CHF process minimally affected left ventricular size and function. At the level of the myocyte, chronic beta- 1-recep for blockade prolonged the contraction interval and thereby increased myocyte shortening. These unique results suggest that a contributory mechanism for the effects of beta-blockade in the setting of CHF is chronotropic modulation.

Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation.

The mechanism by which beta blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved beta-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually beta-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the beta-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the beta-blocked group. We conclude that chronic beta blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements.

Improved baroreflex control of the heart rate with chronic beta-adrenergic blockade in mild hypertension

Improved baroreflex control of the heart rate with chronic beta-adrenergic blockade in mild hypertension

Effects of propranolol administration on cardiac responses to burn injury.

Previous studies showing that propranolol upregulates beta-adrenergic receptors and protects against myocardial ischemia led us to hypothesize that preburn propranolol would protect against postburn cardiac dysfunction. Guinea pigs were treated with propranolol 3 mg/kg/day for 14 days, then deeply anesthetized and subjected to a 45% 3 degrees scald burn; eight guinea pigs treated with propranolol served as the control group (group 1). Burned guinea pigs were resuscitated with Ringer's lactate given as either 4 ml (group 2, N = 8), 6 ml (group 3, N = 10), or 8 ml (group 4, N = 6) per kg/% burn. Guinea pigs treated for 14 days with vehicle (water) were subjected to either sham burn (non-propranolol control, group 5, N = 10) or burn and treatment (group 6, N = 10) as described for group 2. Fluid resuscitation in non-propranolol-treated guinea pigs failed to overcome burn-induced cardiac deficits, as indicated by significantly lower left ventricular pressure, 86 +/- 2 versus 62 +/- 3 mm Hg; +dP/dt max, 1365 +/- 43 versus 1110 +/- 44 mm Hg/sec; -dP/dt max, 1184 +/- 31 versus 881 +/- 40 mm Hg/sec, p < 0.001. Burn-mediated cardiac defects occurred in all propranolol-treated guinea pigs regardless of the fluid volume given. Our data show that (1) propranolol did not protect against burn-induced cardiac dysfunction, and (2) chronic beta-adrenergic blockade increases postburn fluid requirements for maintenance of cardiodynamic stability and for survival.

Assessment of ventricular performance after chronic beta-adrenergic blockade in the marfan syndrome

Morbidity and mortality in the Marfan syndrome mainly result from dilation of the aortic root leading to aortic valve regurgitation, dissection or rupture.’ It has been proposed that by decreasing the inotropic state of the heart, the reduction in impact force of ejected blood on the aortic wall may reduce aortic root dilation and prevent related complications.* This has been the hypothesis for the successful use of @-adrenergic blockers in this disease.3+4 By constructing ventricular contractile performance curves using left ventricular ejection forcq5y6 we confumed that this mechanism is operative during chronic fl-adrenergic blockade’s modulation of aortic root growth rate in patients with the Marfan syndrome. The study cohort comprised 5 male and 4 female patients (age range 10 to 18 years, mean 24.7) with the Marfan syndrome, as diagnosed by a clinical geneticist. AN patients underwent echocardiographic and Doppler evaluation with simultaneous heart rate and bloodpressure determinations. Echocardiograms were analyzed utilizing the Dextra D-200 digitization system. After baseline studies, patients were treated with oral atenolol, which was clinically titrated to a goal of 2 mg;lkg;lday (usually in 2 divided doses). After a minimum treatment period of 6 weeks, the patients underwent reevaluation. Left ventricular ejection force was determined by the method of Isaaz et al,’ using the simplified equation described by Lloyd and Donnerstein.6 Left ventricular ejection force was computed from blood density, the

Myocardial Adaptation to Chronic Propranolol Therapy in Diabetic Rats

The myocardial adaptation to chronic beta-adrenergic blockade was explored in diabetic and control female Wistar rats. Propranolol was administered by intraperitoneal injection, 30 mg/kg every 12 h. Treatment began 2 months after streptozotocin injection and at a comparable time in controls. Diabetes reduced the heart rate by 90 beats/min; propranolol decreased the heart rate by 30 beats/min further in diabetic rats. Propranolol reduced the heart rate by 100 beats/min in controls. Study of isolated ventricular papillary muscle showed qualitatively similar effects of propranolol in control and diabetic animals. Diabetes resulted in prolonged contraction duration and decreased shortening velocity; both developed tension and peak shortening were unchanged. In contrast, propranolol resulted in prolonged contraction duration but no change in shortening velocity; both developed tension and peak shortening were increased. The shortening of isometric relaxation in response to norepinephrine was exaggerated with propranolol therapy in control but not diabetic rats. These findings indicate that the myocardial adaptation to chronic beta-blockade results in increased developed tension and increased extent of muscle shortening in vitro, and differs qualitatively from the adaptation to diabetes.

Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.

Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size.

Effect of beta-adrenergic blockade on myocardial function and energetics in congestive heart failure. Improvements in hemodynamic, contractile, and diastolic performance with bucindolol.

The hemodynamic effects of beta-adrenergic blockade with bucindolol, a nonselective beta-antagonist with mild vasodilatory properties, were studied in patients with congestive heart failure. Fifteen patients (New York Heart Association class I-IV) underwent cardiac catheterization before and after 3 months of oral therapy with bucindolol. The left ventricular ejection fraction increased from 0.23 +/- 0.12 to 0.29 +/- 0.14 (p = 0.007), and end-systolic elastance, a relatively load-independent determinant of contractility, increased from 0.60 +/- 0.40 to 1.11 +/- 0.45 mm Hg/ml (p = 0.0049). Both left ventricular stroke work index (34 +/- 13 to 47 +/- 19 g-m/m2, p = 0.0059) and minute work (5.5 +/- 2.2 to 7.0 +/- 2.6 kg-m/min, p = 0.0096) increased despite reductions in left ventricular end-diastolic pressure (19 +/- 8 to 15 +/- 5 mm Hg, p = 0.021). There was an upward shift in the peak + dP/dtmax-end-diastolic volume relation (p = 0.0005). These data demonstrate improvements in myocardial contractility after beta-adrenergic blockade with bucindolol. At a matched paced heart rate of 98 +/- 15 min-1, the time constant of left ventricular isovolumic relaxation was significantly reduced by bucindolol therapy (92 +/- 17 versus 73 +/- 11 msec, p = 0.0013), and the relation of the time constant to end-systolic pressure was shifted downward (p = 0.014) with therapy. The slope of the logarithm left ventricular end-diastolic pressure-end-diastolic volume relation was unchanged (p = 0.51) after bucindolol. These data suggest that chronic beta-adrenergic blockade with bucindolol improves diastolic relaxation but does not alter myocardial chamber stiffness. Myocardial oxygen extraction, consumption, and efficiency were unchanged despite improvement in contractile function and mechanical work. Thus, in patients with congestive heart failure, chronic beta-adrenergic blockade with bucindolol significantly improves myocardial contractility and minute work, yet it does not do so at the expense of myocardial oxygen consumption. Additionally, bucindolol improves myocardial relaxation but does not affect chamber stiffness.

Adrenergic modulation of potassium metabolism in uremia

The effect of chronic beta adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% of VO2 max) was examined in seven end-stage renal patients who were being maintained on chronic dialysis treatment. Subjects participated in three study protocols: 1) exercise alone, 2) exercise plus propranolol (a nonselective beta-1, beta-2 antagonist), and 3) exercise plus metoprolol (a specific beta-1 antagonist). The basal potassium concentration was similar in all three studies and averaged 4.95 +/- 0.12 mEq/liter. During Study 1 (exercise alone), plasma potassium rose by 0.26 +/- 0.09 mEq/liter. During exercise with propranolol, plasma K concentration rose significantly higher (delta plasma K = 0.44 +/- 0.26 mEq/liter; P less than 0.05 vs. exercise alone). In contrast, the rise in plasma K during exercise with metoprolol (delta plasma K = 0.20 +/- 0.08 mEq/liter) was similar to that observed with exercise alone. Differences in potassium homeostasis between metoprolol and propranolol could not be explained by differences in hemodynamic parameters, levels of potassium regulatory hormones, or acid base status. Thus, the higher rise in potassium concentration during exercise with propranolol could only be explained by adrenergic blockade at the beta-2 receptor site. These results support the concept that adrenergic control of extrarenal potassium homeostasis in dialysis patients is mediated at the beta-2 receptor. Since a deterioration in potassium homeostasis during exercise is observed with beta-2, but not beta-1 blockade, selective beta-1 adrenergic blocking agents may be safer in dialysis patients.

The effect of propranolol on behavioral interactions among adult male cynomolgus monkeys (Macaca fascicularis) housed in disrupted social groupings.

We report here on the social behavior of 30 adult male cynomolgus macaques (Macaca fascicularis), half of which were chronically administered propranolol HCl. All monkeys were maintained in groups of five, fed an atherogenic diet, and subjected to a social manipulation involving repeated disruption of social groups through redistribution of group memberships. One year of intensive behavioral observations were made, involving quantification of 27 kinds of social interaction typically exhibited by this species in captivity. Propranolol treatment resulted in a significant reduction in heart rate and blood pressure. Comparisons between propranolol-treated and untreated monkeys revealed no effects of beta-blockade on social dominance, aggressiveness, or active aspects of affiliation (e.g., grooming). The fact that few behavioral differences were found between conditions in this investigation indicates to us that such effects as were observed may owe as much to chance as to the action of the drug. Overall, these findings suggest that chronic beta-adrenergic blockade has minimal effects on the most prominent features of macaque monkey social behavior, especially those behavioral factors (aggressiveness and competitiveness) associated with risk for coronary disease in this species and in human beings.

Failure of chronic beta-adrenergic blockade to inhibit overfeeding-induced thermogenesis in humans.

The effect of the beta-adrenergic antagonist propranolol on the increase in resting metabolic rate (RMR) induced by overfeeding was examined to determine whether increased beta-adrenergic activity contributes to this response. Six male subjects who were overfed with carbohydrate (1,600 excess kcal/day) for 10 days without drug treatment (control group) had increases (compared with values after 10 days of weight maintenance) in RMR after 6 days [0.24 +/- 0.06 kcal/min (22%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. Eight male subjects were given a weight-maintenance diet for 10 days with oral propranolol treatment (40-60 mg every 6 h) over the last 7 days of this period. Five of these subjects were then overfed for 10 days, and three remained on the weight-maintenance diet; propranolol treatment continued until the end of the study. Propranolol significantly reduced RMR (mean 9%) before the onset of overfeeding but did not prevent increases in RMR after 6 days [0.18 +/- 0.05 kcal/min (16%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. In the subjects who remained on the weight-maintenance diet throughout the study, there was no reversal of propranolol's initial reduction of RMR that would have falsely elevated the overfeeding effect. These data provide further evidence that the increase in RMR induced by overfeeding in humans is not mediated by increased beta-adrenergic activity.

Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.

We ligated the left anterior descending coronary artery for 1 or 2 h in 31 purebred beagles. We did not detect any changes in beta-adrenergic receptor density or affinity when normal and ischemic zones were compared, either in the subendocardium or in the subepicardium. In the ischemic zones, there was a significant decline in all measures of adenylate cyclase activity, including activity mediated by the beta-adrenergic receptor. By contrast, after chronic beta-adrenergic blockade (1.5 mg/kg propranolol i.v. twice daily for 7 d), there was an increase in adenylate cyclase activity stimulated by (-)-isoproterenol relative to adenylate cyclase activity stimulated by guanyl-5'imidodiphosphate (GppNHp) in both normal and ischemic tissue, suggesting that one effect of chronic beta blockade may be to enhance coupling between the stimulatory guanine nucleotide regulatory protein (Gs) and the beta-adrenergic receptor, despite a reduction in the number or function of Gs units. Chronic beta blockade also led to up regulation of beta-adrenergic receptor density in subepicardial regions. After 20 min of reperfusion following 2 h of ischemia, adenylate cyclase activity tended to return to control levels, particularly in the subepicardium, where (-)-isoproterenol-stimulated adenylate cyclase activity was not different from normal myocardium. We conclude that chronic beta-adrenergic blockade may have beneficial effects during prolonged episodes of myocardial ischemia by preserving signal transduction mediated by the beta-adrenergic receptor.

Maximal exercise responses to acute and chronic beta-adrenergic blockade in healthy male subjects

Conflicting data on the alterations in the maximal exercise response to beta blockade (BB) may be the result of differences in the length of time the subject has been on medication, i.e., hours vs days. The purpose of this study was to examine maximal exercise responses during acute and chronic administration of BB. Twenty-eight healthy males, 14 untrained (UT) and 14 involved in a personal training regimen (TR), performed maximal treadmill tests after 1 d and 9 d under three double-blind, randomized conditions: a placebo (PLAC), propranolol (PROP) 80 mg b.i.d., and atenolol (ATEN) 100 mg o.d. Maximal heart rate (HR), oxygen consumption (VO2), ventilation (VE), and treadmill time were significantly reduced by PROP and ATEN after an acute and chronic dose when compared to PLAC (P less than 0.05) in both groups of subjects. Maximal HR was decreased more after 1 d of BB than after 9 d of BB with both PROP and ATEN in the UT subjects and with PROP only in the TR group. VO2max, VEmax, and treadmill time were also less attenuated after 9 d of BB; however, this trend did not reach statistical significance. The nonselective beta blocker, PROP, caused greater reductions in VO2max compared to the selective beta blocker, ATEN, in both groups of subjects. These data indicate that, other than a small change in maximal HR, there is no difference in the exercise response to acute and chronic BB in normal and highly conditioned individuals.

Sympathetic predominance in essential hypertension: a study employing spectral analysis of heart rate variability.

In this study on 91 subjects we tested the hypothesis of an enhanced sympathetic activity in uncomplicated essential hypertension employing spectral analysis of heart rate variability. With this technique the tonic sympathetic and vagal activities and their changes are respectively assessed by the power of approximately 0.1 Hz (low frequency, LF) and approximately 0.25 Hz (respiratory linked, high frequency, HF) components of the spectrum of the beat by beat variability of RR interval. When comparing the 40 subjects with diastolic blood pressure consistently greater than 95 mmHg (hypertensives, Ht), with 35 age-matched controls (diastolic arterial pressure less than 90 mmHg, Nt), we observed that LF was greater and HF smaller in Ht as compared to Nt, thus suggesting an enhanced sympathetic activity and a reduce vagal activity in Ht. Additionally, passive tilt, which in Nt enhances LF [delta = 26 +/- 2 normalized units (nu)] and reduces HF (delta = -22 +/- 2, nu), produced smaller (P less than 0.05) changes in Ht (delta LF = 6.3 +/- 2.7 and delta HF = -7.5 +/- 2.3 nu). Furthermore, the values of LF at rest and the altered effects of tilt on LF and HF were significantly correlated with the degree of the hypertensive state. Chronic beta-adrenergic blockade (atenolol 100 mg once daily for 2 weeks, n = 13) reduced heart rate and blood pressure (from 162/103 to 136/88 mmHg) together with a significant diminution of LF and an increase of HF. Thus, spectral analysis of RR variability appears to be a convenient non-invasive technique to follow the progressive alterations in sympatho-vagal balance present in essential hypertension.