Cardiovascular, sympathetic and adrenal cortical responsiveness of aged fischer-344 rats to stress

While resting, Fischer-344 rats underwent a decrease in heart rate and an increase in diastolic blood pressure and plasma norepinephrine with increasing age. The blood pressure of adult rats increased significantly during a 3 minute immobilization. The blood pressure of old rats failed to increase during stress, decreased to below control level immediately following the termination of stress and they died within 24 hours. Three minutes of stress failed to increase the heart rate of old rats while 30 min of stress produced a small increase in the heart rate, approximately to of the increase seen in younger rats. The old rats showed no decrease in the maximal adrenergic medullary or cortical responses to stress, but they had a prominent 3 min delay in the maximal peak of norepinephrine release. The 30 minute stress caused a greater increase in plasma epinephrine in old rats than in adult rats while it initiated a decrease in beta-adrenergic responses such as heart rate and plasma glucose. The present results indicate that old rats lose their ability to cope with acute stress due to decreased adrenergic responsiveness and increased “shock” reaction.     

Tonic immobility and the alpha-adrenergic system in chickens

In two experiments, groups of $\text{2}\text{1}\text{2}$ to $\text{3}\text{1}\text{2}$ week old chickens were injected with various adrenergic agonists. The relatively low potency alpha agonists (methoxamine, phenylephrine) produced significant decreases in the duration of tonic immobility, while more potent alpha agonists (norepinephrine, methyldopa, clonidine, epinephrine) produced increases in the duration of immobility. Isoproterenol, a beta agonist, had no apparent effect on immobility. These results clearly support the involvement of the alpha-adrenergic system with the immobility response and are discussed in terms of the importance of the adrenergic system for other predator responses such as fight or flight, and the possible differential relations of tonic immobility to alpha₁ and alpha₂ receptors.     

A tale of two mechanisms: A meta‐analytic approach toward understanding the autonomic basis of cardiovascular reactivity to acute psychological stress

A series of meta‐analyses was undertaken to determine the contributions of sympathetic and parasympathetic activation to cardiovascular stress reactivity. A literature search yielded 186 studies of sufficient quality that measured indices of sympathetic (n = 113) and/or parasympathetic activity (n = 73). A range of psychological stressors perturbed blood pressure and heart rate. There were comparable aggregate effects for sympathetic activation, as indexed by increased plasma epinephrine and norepinephrine, and shortened pre‐ejection period and parasympathetic deactivation, as indexed by heart rate variability measures. Effect sizes varied with stress task, sex, and age. In contrast to alpha‐adrenergic blockade, beta‐blockade attenuated cardiovascular reactivity. Cardiovascular reactivity to acute psychological stress would appear to reflect both beta‐adrenergic activation and vagal withdrawal to a largely equal extent.     

Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome

The chronic fatigue syndrome (CFS) has been shown to be associated with orthostatic intolerance and cardiovascular dysregulation. We investigated the cardiovascular responses to combined orthostatic stress and isometric exercise in adolescents with CFS. We included a consecutive sample of 15 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 56 healthy control subjects of equal sex and age distribution. Heart rate, systolic, mean and diastolic blood pressure, stroke index, and total peripheral resistance index were non-invasively recorded during lower body negative pressure (LBNP) combined with two consecutive periods of handgrip. In addition, we measured baseline plasma catecholamines, and recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma epinephrine (P < 0.05) than controls. During LBNP, CFS patients had a greater increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05) and total peripheral resistance index (n.s.) than controls. During handgrip, CFS patients had a smaller increase in heart rate, diastolic blood pressure (P < 0.05), mean blood pressure and total peripheral resistance index (n.s.) than controls. Our results indicate that adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress. This suggests that CFS might be causally related to sympathetic dysfunction.     

Sex differences in the sympatho-adrenal response to isometric exercise

Summary The effects on heart rate, blood pressure, and plasma catecholamines (epinephrine, norepinephrine, dopamine) of sustained isometric contraction (SIC) were studied in six women and nine men. Each subject held a tension equivalent to 30% of maximal handgrip strength until exhaustion. There were no significant differences between women and men in the duration of handgrip. Rise of heart rate and blood pressure were similar for women and men. Considering the absolute plasma levels of each catecholamine, no sex differences was observed at rest and at any time during SIC, except for epinephrine whose concentration was higher in men at first min of SIC. On the other hand, women and men exhibited different adrenergic patterns in response to SIC: in the first min of exercise the plasma level of the three catecholamines increased in men whereas for women plasma catecholamines levels were essentially unaffected. Thus, epinephrine seems to play a minor role in the regulation of heart rate and blood pressure during SIC for women. Another interesting result of our study is that SIC is able to induce an increase in dopamine plasma level for women as well as for men.     

Physiological and behavioral responses of New Zealand hypertensive and normotensive rats to stress

A chronic catheter was inserted into the ventral tail artery of adult male New Zealand hypertensive (NZH) and normotensive (NZN) rats to allow for repeated sampling of blood and measurement of blood pressure and heart rate in conscious animals without handling. Two days after surgery, plasma levels of norepinephrine (NE) and epinephrine (EPI) were similar in NZH and NZN rats while resting and undisturbed in their home cages. Mean arterial blood pressure was significantly higher in NZH rats (166±9 mm Hg) than in NZN rats (124±4 mm Hg) but basal heart rates did not differ (345±8 and 342±14 beats/min, respectively). Increments in plasma levels of NE and EPI and in mean arterial blood pressure and heart rate were similar in NZH and NZN rats following transfer to a shock box and immediately and 10 minutes after exposure to 1 minute of intermittent footshock. Male rats of the two strains also did not differ in their behaviors during tests in an open field arena. These results indicated that NZH and NZN rats do not differ with respect to basal or stress-induced increments in sympathetic-adrenal medullary activity or in several behavioral measures. These results are in striking contrast to previous studies with the Okamoto strain of spontaneously hypertensive (SHR) rats and indicate that genetically determined increases in arterial blood pressure are not necessarily associated with sympathetic-adrenal medullary and behavioral hyperresponsivity to stress.     

Spontaneous wheel running attenuates cardiovascular responses to stress in rats

We investigated the effect of chronic, 10-week spontaneous wheel running (SWR) exercise on stress-induced cardiovascular responses in free-moving male rats, using a biotelemetry system. During cage-switch stress or immobilization stress, blood pressure and heart rate were significantly increased in both the SWR (P<0.001 for each stress) and control groups (P<0.001 for each stress). However the blood pressure response was attenuated significantly in the SWR group (P<0.001) during cage-switch stress, and the blood pressure and heart rate responses were attenuated significantly in the SWR group (P<0.0001 and 0.01, respectively) during immobilization stress. The plasma norepinephrine (NE) response induced by immobilization stress tended to be attenuated in the SWR group, but the groups showed no significant differences in the plasma NE and epinephrine (E) responses to both stresses. These results suggest that daily SWR in rats has beneficial effects in suppressing excessive blood pressure and heart rate responses induced by two different types of stress. The mechanisms responsible for the greater resistance to these stresses in the SWR rats should be investigated further.     

Habituation and sensitization of plasma catecholamine responses to chronic intermittent stress: effects of stressor intensity

Adult male Sprague-Dawley rats were exposed acutely (1 time for 30 minutes) or chronically (30 minutes per day for 27 days) to swim stress in water maintained at either 18 degrees C, 24 degrees C or 34 degrees C. Each rat was prepared with an indwelling tail artery catheter to allow for direct measures of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats per minute) and for remote collection of blood samples before, during and after the 1st or 27th swim stress session. Blood samples were later analyzed for plasma levels of norepinephrine and epinephrine to serve as an assessment of sympathetic-adrenal medullary activity. Compared to handled controls, body weight gain was reduced significantly in rats exposed chronically to swim stress at any of the 3 temperatures. However, baseline values of MAP and HR and plasma levels of norepinephrine and epinephrine were similar in chronically stressed rats compared to their handled controls. The plasma norepinephrine response of rats exposed chronically to either 18 degrees C or 24 degrees C swim stress was significantly greater than that of matched controls stressed for the first time. In contrast, the plasma epinephrine response of chronically stressed rats from these two groups was slightly but not significantly reduced compared to matched controls. For swim stress at 34 degrees C, the plasma norepinephrine and epinephrine responses of chronically stressed rats were reduced significantly compared to controls stressed for the first time. These findings demonstrate that stressor intensity affects sensitization and habituation of plasma catecholamine responses in laboratory rats exposed to chronic intermittent stress.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma catecholamines in fasted and sucrose supplemented rats

Rats were food deprived or given a sucrose supplemented diet for 3 days. Resting plasma catecholamine levels measured remotely from undisturbed rats were not altered by either dietary treatment. However, food deprivation did result in decreases in resting mean arterial blood pressure, heart rate, plasma volume and plasma Na+ concentration. After one minute of intermittent footshock food deprived and sucrose fed rats did not differ from controls with respect to blood pressure, heart rate or plasma catecholamine levels but food deprived rats were less active during footshock and had lower levels of plasma glucose immediately after footshock when compared to controls or sucrose fed rats. Food deprivation and dietary sucrose supplementation have been shown to alter norepinephrine (NE) turnover in specific sympathetic target tissues. Our data indicate that these changes in turnover are not reflected by changes in plasma NE. Therefore, NE turnover rates and plasma NE concentration may not be equivalent indices of sympathetic activity.     

Mechanisms involved in central cardiovascular effects of prostaglandin F2 alpha

Prostaglandin F2 alpha (PGF2 alpha) injected into the cerebroventricular system (icv) of halothane-anesthetized rats increased the arterial blood pressure, heart rate, and rectal temperature. These effects were accompanied by a preferential increase in plasma norepinephrine concentration. Plasma levels of epinephrine, renin, and vasopressin were not changed in the PGF2 alpha-icv-treated rats. Bilateral vagotomy did not affect the PGF2 alpha-induced hypertension and tachycardia nor was there any change in the selective increase in plasma norepinephrine concentration. Hexamethonium pretreatment suppressed, in a dose-response manner, the increases in blood pressure, heart rate, and rectal temperature in response to PGF2 alpha-icv. Plasma norepinephrine and epinephrine levels were not altered by PGF2 alpha-icv in hexamethonium-treated rats, but plasma vasopressin concentration was markedly elevated in all hexamethonium-infused rats. These results suggest that selective central activation of the sympathetic nervous system underlies the profound cardiovascular and temperature responses elicited by central administration of PGF2 alpha.     

Alpha and beta adrenergic sensitivity in trained and untrained albino rats

The effects on the blood pressure and heart rate responses of different adrenergic stimulants (norepinephrine, sympathomim, epinephrine and isoproterenol) and blocking agents (phenoxybenzamine and propranolol) were studied in control (N = 55) and exercising (N = 52) albino rats under anaesthesia. The test rats exercised by regular swimming for 10–14 weeks.Alpha stimulation and beta blocking produced smaller responses while alpha blocking and beta stimulation were followed by greater changes after training as compared with the control animals. The assumption of a modified adrenergic receptor sensitivity could not be substantiated by the results; the observations indicate rather a complex change in the autonomous regulation following regular physical exercise.     

Effects of yohimbine on cerebral blood flow, symptoms, and physiological functions in humans

OBJECTIVE: Increases in adrenergic activity are associated with stress, anxiety, and other psychiatric, neurological, and medical disorders. To improve understanding of normal CNS adrenergic function, CBF responses to adrenergic stimulation were determined. METHODS: Using PET, the CBF changes after intravenous yohimbine, an alpha2-adrenoreceptor antagonist that produces adrenergic activation, were compared with placebo in nine healthy humans. Heart rate, blood pressure, Paco2, plasma catecholamines, and symptom responses were also determined. RESULTS: Among nonscan variables, yohimbine produced significant symptom increases (including a panic attack in one subject), a decrease in Paco2 due to hyperventilation, increases in systolic and diastolic blood pressure, and a trend toward a significant norepinephrine increase. Among scan results, yohimbine produced a significant decrease in whole-brain absolute CBF; regional decreases were greatest in cortical areas. Medial frontal cortex, thalamus, insular cortex, and cerebellum showed significant increases after normalization to whole brain. Medial frontal CBF change was correlated with increases in anxiety. A panic attack produced an increase instead of a decrease in whole-brain CBF. Factors potentially contributing to the observed CBF changes were critically reviewed. Specific regional increases were most likely due in large part to activation produced by adrenergically induced anxiety and visceral symptoms. CONCLUSIONS: This study supports the relationship of anxiety and interoceptive processes with medial frontal, insular, and thalamic activation and provides a baseline for comparison of normal yohimbine-induced CNS adrenergic activation, adrenergically-based symptoms, and other markers of adrenergic function to stress, emotion, and the adrenergic pathophysiologies of various CNS-related disorders.     

Central activation and peripheral function of sympatho-adrenal and cardiovascular systems in the Zucker rat

Electrical stimulation of the hypothalamus in anesthetized lean and obese Zucker rats produced equivalent activation of the sympatho-adrenal system (assessed by plasma norepinephrine [NE] and epinephrine [E] levels) and cardiovascular systems (assessed by monitoring intra-arterial blood pressure and heart rate). Basal plasma E levels were 11% higher and basal heart rates were 20% higher in obese than lean rats. Binding of beta-adrenergic antagonist, [3H] dihydroalprenolol to cardiac membranes was equal but there was a slightly lower affinity for various adrenergic agonists in the hearts of obese compared to lean rats. These results suggest that there are no striking abnormalities in the central pathways for activation of the sympatho-adrenal and cardiovascular systems of obese Zucker rats comparable to those previously described in the peripheral sympatho-adrenal system and other specific organs of these animals [8, 9, 12-15].     

Plasma noradrenaline response to sustained handgrip in patients with essential hypertension

Summary The responses of plasma noradrenaline, arterial blood pressure, and heart rate to sustained handgrip at 30% maximal voluntary contraction were studied in untreated patients with essential hypertension and in healthy subjects of comparable age.There were no significant differences between these two groups in the intensity and duration of handgrip. Increases in heart rate and blood pressure induced by the effort were similar in hypertensive patients and normotensive control subjects, whereas the absolute levels of blood pressure were considerably higher in the patients.In the first 1–2 min of exercise the increases in plasma noradrenaline concentration were similar in both groups. Subsequently, plasma noradrenaline concentration tended to plateau in hypertensive patients while in control subjects it continued to increase. The elevation of plasma noradrenaline in the last minute of effort was, therefore, significantly smaller in hypertensive patients than in the control group.     

Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress.

Blood pressure, heart rate, and circulating levels of norepinephrine, epinephrine, and corticosterone were measured before and during the first or seventh period of immobilization stress (150 min per day) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive male rats. A catheter was inserted into the tail artery of each rat to permit direct measurement of blood pressure and heart rate and serial sampling of blood in conscious, unhandled animals. During the first immobilization, SHR rats had significantly higher circulating levels of norepinephrine, epinephrine, and corticosterone than did WKY rats. One day after the sixth immobilization, basal levels of norepinephrine and epinephrine were significantly higher and mean blood pressure was significantly lower in repeatedly stressed SHRs compared to unstressed SHRs. In addition, adaptation to the repeated stress in SHRs was attended by reduced adrenomedullary secretion and an increased blood pressure response. These results demonstrate that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.     

Changes in hippocampal rhythmic slow activity during instrumental cardiovascular conditioning in the monkey (Macaca mulatta)

Analyses of 4–8 Hz electrical activity (RSA) of the mid-ventral hippocampus, motor activity (M), and blood pressure were carried out during experiments in which three monkeys were operantly conditioned to slow heart rate (HR), to speed HR or during control, no feedback ($\text{FB}$) periods. The results showed that RSA activity was greater during contingent HR (FB) slowing than during HR slowing noncontingent ($\text{FB}$) for all three animals. Motor activity tended to show small changes across conditions; however, it was higher during HR speeding and lower during HR slowing in two animals. There was no differential effect of FB on motor activity for any animal. Blood pressure changes were small and variable throughout conditioning. RSA changes tended to be highly consistent both early and late in conditioning. Results are discussed in terms of attentional and somatic factors that may be operative during instrumental cardiovascular conditioning.     

Neurogenic modification of the vulnerability of the blood-brain barrier during acute hypertension in conscious rats

To study the possible influence of sympathetic adrenergic tone on the blood-brain barrier function during acute hypertension in conscious unrestrained rats with indwelling catheters in the aorta and a jugular vein the blood pressure was increased by noradrenaline, 6-hydroxydopamine (6-OHDA) or baclofen. One or 60 min later the rats were sacrificed and the extravasation of ¹²⁵I labelled albumin determined in the brain. After i. v. injection of noradrenaline the baroreceptor reflex will decrease the sympathetic tone whereas the blood pressure increase induced by the other two drugs is accompanied by an increased sympathetic activity. One minute after a corresponding rise in blood pressure the albumin content in the brain was considerably lower in rats given 6-OHDA than in those given noradrenaline. 60 min after the injection of 6-OHDA or baclofen the extravasation in the brain did not differ despite a considerably more rapid increase in pressure after 6-OHDA. Pretreatment with clonidine increased the blood-brain barrier dysfunction in rats given 6-OHDA but not in those given baclofen, probably because the slower rise in pressure facilitates myogenic autoregulation. It is concluded that neurogenic influences on vessel tone can modify the response of the blood-brain barrier during acute hypertension in conscious rats.     

Acute regulation of lymphocyteβ-adrenoceptor activity in pheochromocytoma

Summary The effect of an acute endogeneous catecholamine stimulation on the regulation of lymphocyte-adrenoceptor activity was studied in a patient with pheochromocytoma. Baseline blood pressure, heart rate, adrenoceptor density, and plasma concentrations of epinephrine, norepinephrine, and cyclic adenosine monophosphate were normal. Excessive spontaneous increases of catecholamine concentrations were accompanied by a rise in blood pressure, bradycardia, and an acute up-regulation of-adrenoceptors. Plasma concentrations of cyclic adenosine monophosphate paralleled the increase in receptor density and blood pressure. After normalization of catecholamine plasma levels, blood pressure, and-adrenoceptor density returned to baseline values. This observation adds support to the theory that an acute catecholamine stimulation leads to an acute sensitization of the-adrenoceptor-adenylatecyclase-cyclic-adenosine-monophosphate system leading to blood pressure elevation.Abbreviations B_max maximal binding sites per cell - cAMP cyclic-adenosine monophosphate - E epinephrine - HR heart rate - KD dissociation constant - MAP mean arterial blood pressure - NE norepinephrine - AAS -adrenoceptor-adenyl-atecyclase-cAMP system To Professor Dr. N. Zöllner in honor of his 65th birthday     

Physiological responses to acute stress in alloxan and streptozotocin diabetic rats

Physiological responses to acute stress were assessed in alloxan diabetic, streptozotocin diabetic and control laboratory rats. Rats were prepared with indwelling tail artery catheters to allow for direct measurement of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats per minute) and remote sampling of blood. Within 24 hours after surgery, basal values of MAP and HR were determined. Two days after surgery, rats were subjected to 5 minutes of intermittent footshock. Blood samples were collected before footshock stress and immediately and 15 minutes after termination of footshock. Plasma levels of norepinephrine (NE) and epinephrine (EPI) increased significantly above basal values in all animals exposed to acute footshock stress. However, in approximately one-half of alloxan and streptozotocin diabetic rats, plasma levels of EPI under basal conditions and following footshock stress were elevated significantly compared to controls and the remaining diabetic animals. We have denoted these subgroups of diabetic animals as reactive responders (plasma EPI greater than controls) and nonreactive responders (plasma EPI similar to controls), respectively. Plasma levels of NE under basal conditions and following footshock stress were similar in reactive responders and nonreactive responders compared to matched controls. Baseline blood glucose levels were elevated in alloxan and streptozotocin diabetic rats compared to controls. Blood glucose levels increased reliably in all animals following footshock stress. Basal MAPs were reduced significantly in both subgroups of alloxan and streptozotocin diabetic rats compared to matched controls. In contrast, resting HRs were similar between diabetic rats and their corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of breathing during acute change in cardiac preload in a patient with partial cardiopulmonary bypass

We recently had the opportunity to investigate the ventilatory effects of changing the rate of venous return to the heart (and thus pulmonary gas exchange) in a patient equipped with a venous-arterial oxygenated shunt (extracorporeal membrane oxygenation (ECMO) support). The presence of the ECMO support provided a condition wherein venous return to the right heart could be increased or decreased while maintaining total aortic blood flow and arterial blood pressure (ABP) constant. The patient, who had received a heart transplant 12 years ago, was admitted for acute cardiac failure related to graft rejection. The clinical symptomatology was that of right heart failure. We studied the patient on the 4th day of ECMO support, while she was breathing spontaneously. The blood flow diverted through the ECMO system represented 2/3 of the total aortic flow (4 l min⁻¹). With these ECMO settings, the baseline level of ventilation was low (3.89 ± 0.99 l min⁻¹), but PET_CO2$\text{PE}{\text{T}}_{\text{C}{\text{O}}_2}$ was not elevated (37 ± 2 mmHg). When Pa_CO2$\text{P}{\text{a}}_{\text{C}{\text{O}}_2}$ in the blood coming from the ECMO was increased, no stimulatory effect on ventilation was observed. However, when the diversion of the venous return to the ECMO was stopped then restored, minute ventilation respectively increased then decreased by more than twofold with opposite changes in PET_CO2$\text{PE}{\text{T}}_{\text{C}{\text{O}}_2}$. These maneuvers were associated with large changes in the size of the right atrium and ventricle and of the left atrium. This observation suggests that the change in venous return affects breathing by encoding some of the consequences of the changes in cardiac preload. The possible sites of mediation are discussed.