Short term effectiveness and hemodynamic actions of guanadrel, a new sympatholytic drug.
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Biomedical subjects
Publications and source records attributed to S Julius.
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Mounting evidence shows that elevated heart rate is associated with a greater risk of developing hypertension and atherosclerosis and that it is a potent predictor of cardiovascular morbidity and mortality. These relationships have been shown not only in general populations but also among hypertensive individuals, with important implications for the treatment of hypertension. In spite of this evidence heart rate has been overlooked as a risk factor, but the fact that in most studies the risk related to fast heart rate remained highly significant after controlling for major risk factors for atherosclerosis suggests that it plays a direct role in the induction of the risk. The clustering of several risk factors for coronary artery disease in subjects with fast heart rate suggests that sympathetic overactivity accounts for the increased cardiovascular morbidity in subjects with tachycardia. In fact, experimental studies have shown that a heightened sympathetic tone can cause obesity, hyperinsulinemia, and insulin resistance which in the long run can promote the development of atherosclerosis. Moreover, experimental studies in the animal suggest that the heamodynamic disturbances related to high heart rate have a direct impact on the arterial wall promoting the development of atherosclerotic plaques. Preliminary results in the experimental animal and pooled data from intervention studies in patients with myocardial infarction or congestive heart failure suggest that drug-induced reduction of heart rate may be beneficial in several clinical conditions.
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Psychologic studies of hypertension have usually focused on the relationship of anger and anxiety to clinic or laboratory blood pressure (BP). Yet, average blood pressure outside of the clinic has proven to be a more important predictor of hypertensive complications. In this study, we have isolated two groups of borderline hypertensives--one group that maintained high blood pressure outside of the clinic and another whose average BP returned to normal at home. All 33 subjects were given psychometric instruments for measuring various components of anger and anxiety: Spielberger's State-Trait Personality Inventory, the Anger Expression Scale, and the State Anger Reaction Scale. The high home BP group reported greater intensity of anger, although they suppressed their expression of anger to a greater extent. The groups did not differ in anxiety. Also, blood pressure variability was not different between the two groups. It is suggested that the psychologic differences found in the group of higher-risk borderline hypertensives may, through autonomic arousal, contribute to the later development of established hypertension.
This study tested the hypothesis that the Type A behavior pattern and its components are associated with increased activity of the sympathetic nervous system. To do this, we employed two new markers of sympathetic tone--pupil size and platelet catecholamine content. Thirty-three healthy males were blindly rated for Type A behavior and verbal stylistic components by Structured Interview. Adrenergic tone to the pupils was assessed from pupil diameter recorded by infrared television pupillometry, and pupil alpha-adrenergic sensitivity was estimated from mydriatic response to ophthalmic phenylephrine. Platelet epinephrine and norepinephrine contents were assayed because these levels are associated with chronic, long-term circulating catecholamine levels. The results showed Type As had consistently larger pupil diameters than Type Bs (p = 0.03, 0.03, and 0.01). There was no difference in pupillary response to phenylephrine instillation between groups. Platelet epinephrine content was greater in Type A subjects (chi 2 = 4.25, p less than 0.04, t = 1.6, p = 0.06). Only the component of explosiveness was modestly associated with resting pupil size, and no components significantly predicted platelet catecholamines. We conclude that the results of these two new markers of autonomic activity, namely, pupil size and platelet epinephrine, suggest that Type A behavior is characterized by increased sympathetic nervous system tone although we cannot rule out the possibility of decreased activity of the parasympathetic nervous system.
Type A coronary-prone behavior has been characterized previously by cardiovascular hyperreactivity to laboratory stressors. The objectives of this study were: 1) to determine whether cardiovascular patterns under more naturalistic circumstances in the field were altered in Type A subjects, and 2) to determine whether these field patterns paralleled cardiovascular patterns to a series of stressors in the laboratory. Thirty-three healthy Type A and B men underwent 24-hr ambulatory blood pressure and heart rate monitoring during a normal day of activities. These subjects were also tested in the laboratory for blood pressure and heart rate responses to a series of stressor tasks: 1) cognitive (mental arithmetic), 2) perceptual motor (reaction time), and 3) physical (handgrip). Type A behavior and stylistic components were rated by structured interview. All studies were conducted double blindly. Type A subjects demonstrated greater cardiovascular reactivity to the laboratory cognitive stressor, but there was a mixture of differences between As and Bs in variability of ambulatory blood pressure and heart rate during different periods of the day. Yet, there were no differences in average blood pressure levels. The components of verbal competition and loudness of voice were positively associated with elevated average blood pressure and variability in the field, respectively, but not with laboratory hyperreactivity. Thus, this study confirmed laboratory-induced cardiovascular hyperreactivity in Type A behavior but, within its limitations, did not find a similarity between laboratory and field cardiovascular response patterns in these behavioral groups. The ambulatory blood pressure monitoring findings in the component groups may have prognostic significance and deserve further study.
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