Disparate hemodynamic and sympathoadrenergic responses to isometric and mental stress in essential hypertension

The hemodynamic and sympathoadrenergic responses during isometric handgrip and mental arithmetic tests were compared in 18 patients with mild essential hypertension. Mean blood pressure increased significantly after both maneuvers (27% during isometric stress and 10.7% during mental stress), but the increase was significantly higher during isometric stress (p less than 0.001). Both stressors increased the heart rate (p less than 0.001) and cardiac output (p less than 0.001). However, the total peripheral resistance behaved differently, for it increased during isometric stress (p less than 0.05) and remained unchanged during mental stress. Both stressors increased the epinephrine levels (p less than 0.005), but only isometric stress increased the norepinephrine levels (p less than 0.001). It is concluded that both stressors increase cardiac output by way of an increase in heart rate, but isometric stress also increases total peripheral resistance and thus causes a greater increase in arterial pressure. Isometric stress activates both the adrenergic and noradrenergic systems, thereby accounting for the exaggerated response in arterial pressure, whereas mental stress stimulates the adrenergic system only.     

Effects of acute carbohydrate administration on central and peripheral hemodynamic responses to mental stress.

Essential hypertension is closely related to conditions with impaired glucose tolerance and hyperinsulinemia. To evaluate a possible interaction between the sympathetic nervous system and carbohydrate ingestion on the circulatory responses to psychosocial stress, we compared the hemodynamic effects of an oral glucose challenge with those observed after placebo in 10 glucose-tolerant, normotensive young men at rest and during standardized mental stress. After glucose, resting cardiac output increased by 20% (p less than 0.05), which was mainly due to an increased heart rate (+14%; p less than 0.001). Since total peripheral resistance decreased by 13% (p less than 0.02), mean arterial pressure was unaffected by glucose. In spite of this, glucose loading was associated with a slight increase in systolic blood pressure and a gradual decrease of diastolic blood pressure. Resting forearm blood flow was unaffected by glucose. The stress response after placebo was characterized by the expected increase in cardiac output and mean arterial pressure, and an unchanged total peripheral resistance. By contrast, in the postprandial state the pressor response to stress was solely dependent on an increased systemic vascular resistance, and cardiac output was unaffected by stress. After glucose, the stress-induced muscular vasodilation in the forearm was reduced to 40% of that observed after placebo (p less than 0.01). Thus, acute carbohydrate administration has significant hemodynamic effects in humans. Furthermore, during the postprandial period there is a marked alteration of the pattern of the circulatory responses to psychosocial stress, characterized by attenuated muscular vasodilation and a rise in systemic vascular resistance.     

Consistency of hemodynamic responses to cold stress in adolescents

Laboratory research on hypertension often is performed with cold stress to elicit vasoconstriction and increases in blood pressure. Several studies have shown that cardiovascular responses to the cold pressor test predict the development of hypertension. We extended this research by comparing cardiovascular responses to a traditional forehead cold pressor test and a naturalistic whole-body cold exposure. We evaluated blood pressure and impedance cardiographic measures of cardiac output and total peripheral resistance in healthy black (n=69) and white (n=47) adolescents (mean age, 14.7 years) during forehead cold pressor (3 degrees C to 4 degrees C) and passive whole-body exposure to a cold chamber (8 degrees C to 10 degrees C). Both tasks elicited increases in vascular resistance and blood pressure, but forehead cold elicited an increase in cardiac output, whereas whole-body cold elicited a decrease in cardiac output (P<0.05). Consistent with previous research, there was a tendency toward greater vasoconstrictive reactivity to cold stress in blacks than in whites, particularly during whole-body cold exposure (P<0.05). Cardiovascular reactivity correlated significantly between tasks, but substantial intertask consistency occurred only for cardiac and vascular reactivity in male subjects (r>0.30) but not in female subjects (r<0.15). These gender differences might reflect diminished adrenergic receptor function in female subjects. We conclude that whole-body cold exposure offers a viable, relatively naturalistic alternative to traditional cold pressor tests for the assessment of cardiovascular reactivity.     

Effects of hyperinsulinemia on sympathetic responses to mental stress

In a recent study, we could not find evidence to support the hypothesis that insulin activates the sympathetic nervous system (SNS) during a hyperinsulinemic glucose clamp procedure. Mental stress tests (MST), however, may be used to detect differences in blood pressure and SNS activity that are not present during baseline or resting conditions. In this study, we aimed to investigate the effects of hyperinsulinemia during glucose clamp on blood pressure and sympathetic responses to mental stress.Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant. Insulin concentration increased from 119 ± 10 pmol/L to 752 ± 65 pmol/L. We observed highly significant increases in blood pressure and heart rate in response to MST, but neither insulin nor saline solution infusions affected these responses. During MST-1, norepinephrine increased by 461 ± 165 pmol/L (mean ± SEM) and epinephrine by 218 ± 76 pmol/L. During MST-2 the changes were 372 ± 112 pmol/L and 187 ± 60 pmol/L, respectively. The norepinephrine (P = .8) and epinephrine (P = .7) responses were unchanged by insulin. Thus, there were similar increases in blood pressure, heart rate, and plasma catecholamine concentrations in arterialized venous blood in response to MST despite the infusion of insulin. A possible time effect was excluded by including a saline solution control group (n = 7) that showed almost identical results.Our results suggest that acute hyperinsulinemia during isoglycemic glucose clamp does not interfere with cardiovascular or sympathetic responses to mental stress.     

Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses

OBJECTIVES: This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography. BACKGROUND: Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age 59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure. RESULTS: Mental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rdeltaSBP = -0.26, rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.     

Effect of calcium channel blockers on hemodynamic responses to defibrillation

The hemodynamic response to sequences of ventricular fibrillation and defibrillation includes an adrenergic component that is important for the maintenance of blood pressure after successful defibrillation. Because calcium channel blocking drugs have antiadrenergic effects, we hypothesized that they might blunt the adrenergic response to defibrillation. Ventricular fibrillation was induced in 35 closed-chest dogs. Each received 4 to 7 direct current transthoracic shocks at three energy levels to determine defibrillation energy requirements. Heart rate and blood pressure were recorded. Energy sequences were repeated after 45 minutes of no intervention (control, n = 5) or after 45-minute infusions of diltiazem (0.1 mg/kg/min, n = 10), verapamil (0.1 mg/kg bolus plus 0.01 mg/kg/min, n = 10), or nifedipine (40 micrograms/min for 3 minutes plus 2 to 20 micrograms/min adjusted to maintain a 10 mm Hg drop in mean arterial pressure, n = 10). Our results show that the normal post-shock rise in mean arterial pressure was blunted by the calcium channel blockers diltiazem (systolic arterial pressure at 15 and 60 seconds post-shock, pre-drug versus post-drug: 102 +/- 9 versus 64 +/- 9 mm Hg and 113 +/- 10 versus 87 +/- 6 mm Hg; p less than 0.05) and verapamil (108 +/- 9 versus 78 +/- 12 mm Hg and 113 +/- 7 versus 90 +/- 10 mm Hg, p less than 0.05). There were no differences in blood pressure responses after nifedipine treatment or no drug. Heart rate responses were not altered by diltiazem or verapamil; after nifedipine administration, post-shock heart rates were slower.(ABSTRACT TRUNCATED AT 250 WORDS)     

Infusion of epinephrine augments pressor responses to mental stress.

Circulating epinephrine may facilitate neural release of norepinephrine both during and after periods of sympathoadrenal activation by stimulation of prejunctional beta-adrenergic receptors. The present study was undertaken to examine possible effects and aftereffects of epinephrine on the hemodynamic reactivity to mental stress. To this end, two strictly standardized mental stress tests were performed in 14 normotensive men during and 1 hour after double-blind infusion of epinephrine (50 ng x kg-1 x min-1) or placebo given in random order. During epinephrine infusion, the systolic pressor response to psychosocial stress was augmented (+17 versus +10 mm Hg during epinephrine and placebo, respectively; p = 0.02). This was associated with an attenuated post-stress recovery, with the result that the stress exposure induced a prolonged elevation of systolic blood pressure. Heart rate was elevated and diastolic blood pressure lowered during epinephrine infusion without any change in the reactivity to stress. One hour after the end of the epinephrine infusion resting heart rate was still maintained on a higher level independently of level of arousal, but heart rate and blood pressure responses to stress were unaffected. The findings are consistent with the hypothesis that high circulating epinephrine levels amplify pressor responses to mental stress but do not support the suggestion that short-term infusion of epinephrine causes prolonged augmentation of blood pressure responses to psychosocial stress.     

Acute cholesterol responses to mental stress and change in posture.

BACKGROUND--Serum lipid levels vary widely within individuals, but the causes of these fluctuations are poorly understood. One area of research concerns elevations in cholesterol concentration in response to emotional stress. In a laboratory-based experiment, we compared the effects of acute mental stress and postural change (standing) on serum cholesterol concentration. In addition, plasma volume was indirectly monitored to determine whether cholesterol changes with mental stress, if present, were a function of hemoconcentration. METHODS--Twenty-six men attended two laboratory sessions, each consisting of baseline (30 minutes), task (20 minutes), and recovery (30 minutes) periods. Subjects rested in the supine position during the baseline and recovery periods. During the task period of one session, subjects performed a mental task (Stroop test and mental arithmetic); during the other session, the subjects stood for the task period. RESULTS--Both mental stress and standing elicited significant elevations in heart rate, blood pressure, and plasma catecholamine concentrations, relative to the baseline and recovery periods. Both the mental and orthostatic tasks also significantly increased serum cholesterol concentration (by 0.10 and 0.57 mmol/L [3.7 and 21.9 mg/dL], respectively), as well as hemoglobin level and hematocrit. Cholesterol elevations with standing were reversible, while those resulting from mental stress persisted through the recovery period. When values were corrected for concomitant hemoconcentration, no net change in serum cholesterol level occurred during either task. CONCLUSIONS--Acute mental stress can produce rapid elevations in serum cholesterol concentration. It can also increase hemoglobin concentration and hematocrit (ie, reduce plasma volume). Therefore, increases in serum cholesterol level after acute mental stress are analogous to those with standing and may reflect hemoconcentration rather than altered lipoprotein metabolism.     

Hemodynamic and endocrine effects of mental stress in untreated borderline hypertension

Mental arithmetic and mirror tracing were compared in 40 untreated patients with borderline hypertension, tested in random sequence in standardized protocols. Both tasks significantly increased systolic and diastolic blood pressure, heart rate, cardiac index, plasma renin, and decreased peripheral resistance. Mental arithmetic also increased cholesterol, triglycerides and HDL; plasma catecholamines were not changed significantly. Lipid changes were correlated with blood pressure changes. These methods will be useful in exploring the relationships between hemodynamic reactivity to stress, and the presence and progression of atherosclerosis, as well as testing the effects of antihypertensive drugs on stress-induced changes that may influence atherosclerotic complications of hypertension.     

Effect of morphine on the hemodynamic and neuroendocrine responses to hemorrhage in conscious rats

We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Sirén: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 ml/300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a minithermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to saline-treated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 ml/300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.     

Role of sympathetic nerve fibers in hemodynamic responses to stress in rats]

Hemodynamic responses to acute stress exposure were studied in normotensive control (C) and chronically sympathectomized (S) rats. Male Sprague-Dawley rats received daily sc injections of either saline (C) or guanethidine (S) from 1 to 13 weeks of age. Doppler flow probes were then implanted for the measurement of blood velocity in the sub-diaphragmatic aorta, superior mesenteric artery and distal aorta (hindquarters). After 10 days of recovery and 24 hours before the study, the caudal artery was cannulated. In the conscious freely moving rats, mean arterial pressure (MAP), heart rate (HR) and indices of regional blood flows and vascular conductances (G as blood flow/MAP ratio) were recorded beat to beat, before and during emotional stress (jet of air for 2 min). In basal conditions, mean values of MAP and HR were similar in C (107 +/- 2 mmHg; 399 +/- 8 bpm, n = 9) and S (106 +/- 3 mmHg; 384 +/- 12 bpm, n = 7) rats. The effects of stress on MAP, HR, aortic (AoG), mesenteric (MeG) and hindquarters (HqG) vascular conductances are expressed as percentage changes from baseline (delta): [table: see text] These results highlight the role of vascular sympathetic nerves in pressor responses and systemic and mesenteric vasoconstrictions induced by stress in the rat. They also indicate that vasodilatation in the hindquarters vascular bed is not secondary to withdrawal of sympathetic vasoconstrictor tone but rather to active phenomena which do not involve the stimulation of vascular beta 2-adrenoceptors by neuronal catecholamines nor the release of vasodilator cotransmitters from the sympathetic nerve endings.     

Sinoaortic denervation does not increase cardiovascular/endocrine responses to stress.

Sinoaortic baroreceptor denervation is reported to produce exaggerated centrally derived cardiovascular and endocrine responses. We examined the effect of sinoaortic denervation (SAD) on the cardiovascular and endocrine responses to two acute stressors, footshock and immobilization, in male Sprague-Dawley rats. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and plasma levels of oxytocin (OT) and vasopressin (VP). Baseline MAP was elevated in the SAD group (approximately 25 mm Hg) and footshock stress increased arterial pressure equivalently in both groups. This stress caused tachycardia and increased plasma OT, with a tendency for the SAD group to show blunted responses. Immobilization increased HR but caused no change in MAP and no significant difference between the groups. This form of stress also increased plasma OT, and again the SAD group showed a diminished response. Plasma VP was not significantly altered by either stressor. The results of these studies indicate that SAD does not uniformly increase the cardiovascular and endocrine responses to all stressors or centrally derived stimuli. These results also suggest that the lack of an increase in plasma VP is not related to baroreceptor-mediated inhibition of secretion under stressful conditions.     

Cardiovascular and sympathetic nervous responses to mental stress in hyperthyroid patients.

We measured the cardiovascular and sympathetic nervous responses to mental stress in subjects with hyperthyroidism. Ten hyperthyroid subjects and 10 age- and sex-matched normal subjects performed mental arithmetic. At rest, the heart rate was higher in hyperthyroid subjects than in normal subjects, but systolic blood pressure, plasma norepinephrine, and epinephrine concentrations did not differ between the two groups. Systolic blood pressure and heart rate during stress, and the changes in blood pressure and in plasma epinephrine concentration from rest to stress, were higher in hyperthyroid subjects than in normal subjects. Therefore, cardiovascular and adrenal responses to mental stress were abnormally high in subjects with hyperthyroidism.     

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

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