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Alan Kim Johnson

Publications and source records attributed to Alan Kim Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory cytokines and hypothalamic activation in rats with ischemia-induced heart failure.

Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating levels of tumor necrosis factor (TNF)-alpha in heart failure (HF) rats. TNF-alpha and other proinflammatory cytokines activate neurons in the paraventricular nucleus (PVN) of hypothalamus, including corticotropin-releasing hormone (CRH) neurons, by inducing cyclooxygenase (COX)-2 activity and synthesis of prostaglandin E2 by perivascular cells of the cerebral vasculature. We tested the hypothesis that systemic treatment with a MR antagonist would reduce hypothalamic COX-2 expression and PVN neuronal activation in HF rats. Rats underwent coronary ligation to induce HF, confirmed by echocardiography, or sham surgery, followed by 6 weeks treatment with eplerenone (30 mg/kg per day, orally) or vehicle (drinking water). Eplerenone-treated HF rats had lower plasma TNF-alpha, interleukin (IL)-1beta and IL-6, less COX-2 staining of small blood vessels penetrating PVN, fewer PVN neurons expressing Fra-like activity (indicating chronic neuronal activation), and fewer PVN neurons staining for TNF-alpha, IL-1beta, and CRH than vehicle-treated HF rats. COX-2 and CRH protein expression in hypothalamus were 1.7- and 1.9-fold higher, respectively, in HF+vehicle versus sham+vehicle rats; these increases were attenuated (26% and 25%, respectively) in HF+eplerenone rats. Eplerenone-treated HF rats had less prostaglandin E2 in cerebrospinal fluid, lower plasma norepinephrine levels, lower left ventricular end-diastolic pressure, and lower right ventricle/body weight and lung/body weight ratios, but no improvement in left ventricular function. Treatment of HF rats with anticytokine agents, etanercept or pentoxifylline, produced very similar results. This study reveals a previously unrecognized effect of MR antagonism to minimize cytokine-induced central neural excitation in rats with HF.

Animals↗
PubMed2006

Lesions of the anteroventral third ventricle region exaggerate neuroendocrine and thermogenic but not behavioral responses to a novel environment.

Mild psychological stressors provoke an acute rise in core temperature (T(C)), stimulate the hypothalamo-pituitary-adrenocortical (HPA) axis, and induce various stress-related behaviors. In the present study, we examined the effect of ablation of the anteroventral third ventricle region (AV3V) on both physiological and behavioral responses to a novel environment. T(C) was monitored in male Sprague-Dawley rats, with either sham or AV3V lesions, during a 5-h exposure to a novel environment. Trunk blood was collected, in a second group of rats, for the assessment of plasma levels of ACTH and corticosterone. Novelty-induced grooming and rearing behaviors were assessed in a third group of animals. T(C) was elevated in all animals after 30 min in the novel environment, but the rise was exaggerated in rats with AV3V lesions ( approximately 0.5 degrees C). AV3V-lesion rats maintained a higher core temperature for 2 h before it returned to the same level as the control group. Plasma levels of ACTH and corticosterone were also exaggerated in the AV3V lesion group after 30 min in a novel environment. In contrast to the physiological responses, the behavioral measures of grooming and rearing revealed no differences between the groups. The results from the current study suggest that neurons within the AV3V region exert an inhibitory influence on the HPA axis and fever developed in response to stressful psychological stimuli. They also confirm that the physiological and hormonal components of the stress response are independent of certain behavioral measures of stress.

Adrenocorticotropic Hormone↗
PubMed2006

11beta-hydroxysteroid dehydrogenase type 2 activity in hypothalamic paraventricular nucleus modulates sympathetic excitation.

Aldosterone stimulates the sympathetic nervous system by binding to a select population of brain mineralocorticoid receptors (MR). These MR have an equal affinity for corticosterone that is present in substantially higher concentrations, but are held in reserve for aldosterone by activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2), which converts corticosterone to an inactive metabolite. Thus, colocalization of MR and 11beta-HSD-2 activity may help identify brain regions that mediate the effects of aldosterone. The present studies tested the hypothesis that 11beta-HSD-2 activity regulates MR-mediated responses in the paraventricular nucleus (PVN) of the hypothalamus, a forebrain region implicated in sympathetic regulation. Real-time-polymerase chain reaction revealed the presence of 11beta-HSD-2 mRNA in PVN. In anesthetized adult male Sprague-Dawley rats, microinjection of the 11beta-HSD-2 inhibitor carbenoxolone (CBX) into PVN increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. Intracerebroventricular injections of CBX excited PVN neurons and increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. The ability of CBX to increase sympathetic activity by inhibiting 11beta-HSD-2, thereby permitting corticosterone to activate MR, was confirmed by the following: Intracerebroventricular glycyrrhizic acid, another 11beta-HSD-2 inhibitor, mimicked the sympathoexcitatory effects of CBX; the sympathoexcitatory effects of CBX were blocked by spironolactone, a MR antagonist. Neither CBX nor glycyrrhizic acid elicited a response in adrenalectomized rats. These findings suggest that MR in PVN contribute to sympathetic regulation and may be activated by aldosterone or corticosterone (or cortisol in humans) depending on the state of 11beta-HSD-2 activity.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2006

Tachyphylaxis to 5-HT3-receptor-mediated activation of vagal afferents is prevented by co-activation of 5-HT2 receptors.

Functional studies have provided evidence that 5-HT(3) ion-channel receptors (5-HT(3)Rs) on vagal cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) rapidly desensitize upon repeated exposure to selective 5-HT(3)R agonists. G-protein-coupled 5-HT(2) receptors (5-HT(2)Rs) also exist on vagal afferents, although activation of these receptors does not elicit the BJR. However, there is in vivo evidence that 5-HT(2)Rs may regulate the activity of 5-HT(3)Rs. The aim of this study was to determine whether co-activation of 5-HT(2)Rs prevents desensitization of 5-HT(3)Rs mediating the BJR in conscious rats. The principal findings were that (1) tachyphylaxis rapidly developed to the BJR-mediated hemodynamic responses elicited by successive injections of 5-HT(3)R agonists and (2) co-injection of the selective 5-HT(2)R agonist, alpha-methyl-5-HT, prevented tachyphylaxis to the BJR-mediated hemodynamic responses elicited by the 5-HT(3)R agonists. Additional studies provided evidence that (1) tachyphylaxis to the 5-HT(3)R agonists was not due to impairment of the central or efferent processing of the BJR, and (2) the pressor responses elicited by alpha-methyl-5-HT were not responsible for preventing tachyphylaxis to the BJR reflex responses elicited by 5-HT(3)R agonists. These results suggest that the loss of response to 5-HT(3)R agonists is due to desensitization of 5-HT(3)Rs on vagal afferents mediating the BJR and that co-activation of 5-HT(2)Rs prevents the desensitization of these 5-HT(3)Rs.

Animals↗
PubMed2006

Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals.

OBJECTIVE: This study examined the hypothesis that intracellular cGMP stimulates the release of catecholamines from sympathetic nerve terminals (SNTs) in conscious rats. METHODS: Conscious rats were prepared to determine the effects of intravenously-administered agents on heart rate (HR) and mean arterial blood pressure (MAP). RESULTS: Bolus intravenous injections of the membrane-permeable cGMP analogue, 8-(4-chlorophenylthio)-cGMP (8-CPT-cGMP), elicited immediate and pronounced increases in HR before any changes in MAP were observed. In contrast, injections of cGMP did not elicit changes in HR or MAP. The 8-CPT-cGMP-induced tachycardia was markedly diminished by (1) the beta(1,2)-adrenoceptor antagonist, propranolol, (2) the ganglion blocking agent, chlorisondamine, and (3) bretylium, which blocks Ca2+-dependent mobilization of vesicular stores of catecholamines from SNTs. 8-CPT-cGMP also elicited minor falls in MAP in propranolol-treated rats but elicited pronounced falls in MAP in rats treated with chlorisondamine, bretylium, or combined administration of bretylium and the muscarinic receptor antagonist, methyl-atropine. CONCLUSIONS: These findings suggest that (1) intracellular cGMP elicits the release of Ca2+-sensitive and Ca2+-insensitive stores of catecholamines from SNTs in conscious rats, and (2) cGMP-mediated release of catecholamines from SNTs antagonizes cGMP-mediated relaxation of vascular smooth muscle in resistance arteries. Taken together, these findings support the concept that increases in intracellular cGMP levels by atrial natriuretic peptide and endothelium- and cardiac-derived nitric oxide regulate sympathetic control of the heart and the microvasculature of conscious rats via cGMP-dependent release of catecholamines.

Animals↗
PubMed2006

Thermoregulatory behavior is disrupted in rats with lesions of the anteroventral third ventricular area (AV3V).

Core body temperature is maintained through a combination of physiological and behavioral effector mechanisms. While the neural pathways involved in autonomic responses to a heat stress are slowly being unraveled, those controlling behavioral responses have remained elusive. We have recently demonstrated that the tissue that surrounds the anteroventral third ventricular region (AV3V) has an important role in the autonomic response to a heat stress. The purpose of the present study was to determine the impact lesions of the AV3V have on naturally occurring thermoregulatory behaviors. Core temperature was elevated at a constant rate (0.03 degrees C/min) for 90 min using an infrared heat lamp. Animals were videotaped and scored throughout the heating protocol for grooming, escape jumps and postural extension. The frequency of escape jumps and adoption of an extended posture were significantly reduced in AV3V-lesion rats. In contrast, grooming behavior was unaffected by AV3V lesions, although heat-induced salivation was markedly attenuated. These results demonstrate that the AV3V region is pivotal in the regulation of both autonomic and behavioral thermoregulatory effector mechanisms.

Animals↗
PubMed2006

Evidence supporting a functional role for intracellular renin in the brain.

The brain renin-angiotensin system is implicated in the regulation of blood pressure (BP) and fluid homeostasis. Recent studies reveal that 2 forms of renin are expressed in the brain of rodents and humans: secreted prorenin and a nonsecreted intracellular form of active renin (icREN). Although the intracellular action of renin has long been postulated, no data supporting its role in BP regulation has been reported. Therefore, we directly evaluated whether this form of renin has physiological implications for BP regulation by characterizing transgenic mice expressing human icREN driven by the glial fibrillary acidic protein (GFAP) promoter and comparing it with similar mice expressing the secreted form of renin. GFAP-icREN mice express hREN primarily in the brain and at the same level of expression as GFAP-secreted prorenin. Unlike the secreted form, which can be detected in cerebrospinal fluid, no human renin could be detected in the cerebrospinal fluid of GFAP-icREN mice. GFAP-icREN mice were then bred with transgenic mice expressing human angiotensinogen, also driven by the GFAP promoter. Double-transgenic mice expressing either the intracellular renin (2.0+/-0.12 mL/10 g/day) or secreted renin (2.8+/-0.3 mL/10 g/day) exhibited an increase in drinking volume compared with nontransgenic littermates (1.5+/-0.1 mL/10 g/day). Both models exhibited an increase in mean arterial pressure (137+/-5 and 133+/-8 mm Hg, respectively) compared with control littermates (115+/-3 mm Hg), which could be rapidly reduced after ICV injection of losartan. These data support the concept of an intracellular form of renin in the brain, which may provoke functional changes in fluid homeostasis and BP regulation.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

The effects of deoxycorticosterone-induced sodium appetite on hedonic behaviors in the rat.

The authors tested the hypothesis that chronic treatment with a dose of deoxycorticosterone acetate (DOCA) known to elicit a robust sodium appetite can negatively affect the hedonic state of rats. Daily treatment with DOCA with no opportunity to ingest saline produced a rightward shift in the midpoint (effective current 50) of lateral hypothalamic self-stimulation (LHSS) current-response functions and reduced intakes of a palatable sucrose solution. Providing rats with 0.3 M saline during DOCA treatment prevented the rightward shift in LHSS response functions and the decrease in sucrose intake. The authors concluded that a chronic sodium appetite, with no opportunity to attenuate the appetite, can elicit a reduced responsiveness to reward.

Animals↗
PubMed2006

Reduced hedonic behavior and altered cardiovascular function induced by mild sodium depletion in rats.

Interactions among sodium homeostasis, fatigue, mood, and cardiovascular regulation have been described previously. The present study investigates the effects of sodium deficiency on an index of mood (hypohedonia; Experiment 1), cardiovascular function (Experiment 2), and plasma electrolytes (Experiment 3) in rats. Following 48 hr of sodium depletion with a diuretic (furosemide) and a sodium deficient diet, rats displayed hypohedonia evidenced by reduced responding for rewarding electrical brain stimulation into the hypothalamus. Also, sodium depletion produced increased heart rate and reduced heart rate variability. Plasma sodium levels were lower in sodium-depleted rats versus control rats, whereas potassium levels were unchanged. Thus, mild sodium depletion produces hypohedonia and cardiovascular alterations, which has implications for understanding behavioral and cardiovascular consequences of sodium deficiency.

Animals↗
PubMed2006

Downregulation of propranolol-sensitive beta-adrenoceptor signaling after inhibition of nitric oxide synthesis.

The beta-adrenoceptor agonist, isoprenaline, elicits vasodilation and tachycardia in anesthetized rats via activation of propranolol-sensitive beta1- and beta2-adrenoceptors and also by propranolol-insensitive beta1- and beta3-adrenoceptors. The aim of this study was to determine whether the relative contribution of propranolol-sensitive and -insensitive beta-adrenoceptors to the changes in heart rate (HR) and vascular resistances elicited by isoprenaline is altered after blockade of nitric oxide (NO) synthase, in pentobarbital-anesthetized rats. The hemodynamic responses elicited by isoprenaline (0.1 and 0.5 microg kg(-1), i.v.) were determined before and after injection of saline or the NO synthase inhibitor, N(G)-nitro-L-arginine methylester (L-NAME, 50 micromol kg(-1), i.v.), and again after injection of the beta1- and beta2-adrenoceptor antagonist, propranolol (1 mg kg(-1), i.v.). The responses elicited by the above doses of isoprenaline were also determined before and during infusion of the alpha1-adrenoceptor agonist, phenylephrine (3 microg kg(-1) min(-1), i.v.), and again 15-20 min after injection of propranolol (1.0 mg kg(-1), i.v.). Both doses of isoprenaline elicited tachycardia and reductions in vascular resistances. Propranolol eliminated the responses elicited by the lower dose of isoprenaline and substantially diminished the responses elicited by the higher dose of the beta1-, beta2- and beta3-adrenoceptor agonist. The maximal vasodilator responses elicited by both doses of isoprenaline were not diminished whereas the maximal increases in HR were higher after injection of L-NAME. The ability of propranolol to diminish the hemodynamic actions of isoprenaline was substantially diminished in L-NAME-treated rats, whereas propranolol retained its potency in rats that received an equi-pressor infusion of the alpha1-adrenoceptor agonist, phenylephrine. The finding that the maximal vasodilator responses elicited by isoprenaline were not diminished by L-NAME suggests that the vasodilation elicited by this drug was due to direct activation of beta-adrenoceptors on vascular smooth muscle and that the full compliment of isoprenaline-sensitive receptors was not changed after inhibition of NO synthesis. However, these results suggest that the activities of propranolol-sensitive beta-adrenoceptors are downregulated, whereas propranolol-insensitive beta-adrenoceptors are upregulated upon the loss of exposure to endothelial nitrosyl factors.

Adrenergic beta-Agonists↗
PubMed2006

International student exchange and the medical curriculum: evaluation of a medical sciences translational physiology course in Brazil.

The objective of the present study was to conduct a short-term international course on translational physiology for medical students from Wright State University and the University of Iowa. The goals were to 1) provide students with an exposure to the academic, cultural, and medical environments in Brazil; 2) promote awareness of the global medical community; and 3) provide an academic course focused on translational physiology. An evaluation of the students was conducted to determine whether such a short-term course might be useful in the medical curriculum. The 2-wk course was held in the summer of 2005 at the University of São Paulo School of Medicine in Ribeirão Preto, Brazil, for 23 American students. The program included presentations of basic and clinical topics, meetings with medical students, and clinical presentations. The program finished with student attendance at a scientific meeting sponsored by the Brazilian Society of Hypertension. Student surveys evaluated issues related to perceived treatment, Brazilian medical school environment, culture and personal attributes, and career aspirations. The international Medical Sciences Translational Physiology course for medical students provided a brief, but intense, experience. It gave students a picture of the medical environment in Brazil and an appreciation for the differences and similarities in cultures. Most students reported that it was a positive experience that would be beneficial to their careers. In conclusion, a short-term international course provides an efficient means for medical students to experience aspects of global medical science.

Brazil↗
PubMed2005

Activation of serotonergic 5-HT(1A) receptors in the lateral parabrachial nucleus increases NaCl intake.

Previous studies using non-specific serotonergic agonists and antagonists have shown the importance of serotonergic inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) for controlling sodium and water intake. In the present study, we investigated whether the serotonergic 5-HT(1A) receptor subtype in the LPBN participates in this control. Male Holtzman rats had cannulas implanted bilaterally into the LPBN. Bilateral injections of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.1, 1.25, and 2.5 microg/0.2 microl), into the LPBN enhanced 0.3 M NaCl and water intake of rats injected subcutaneously with the diuretic furosemide (10 mg/kg bw) and a low dose of the angiotensin-converting enzyme inhibitor, captopril (5 mg/kg bw). The increase in NaCl intake produced by 8-OH-DPAT injections was reduced in dose-related manner by pre-treating the LPBN with the selective 5-HT(1A) serotonergic antagonist, WAY-100635 (WAY, 1 and 2 microg/0.2 microl). In contrast, WAY did not affect water intake produced by 8-OH-DPAT. WAY-100635 injected alone into the LPBN had no effect on NaCl ingestion. Injections of 8-OH-DAPT (0.1 microg/0.2 microl) into the LPBN also increased 0.3 M NaCl intake induced by 24-h sodium depletion (furosemide, 20 mg/kg bw plus 24 h of sodium-free diet). Serotonin (5-HT, 20 mug/0.2 mul) injected alone or combined with 8-OH-DPAT into the LPBN reduced 24-h sodium depletion-induced 0.3 M NaCl intake. Therefore, the activation of serotonergic 5-HT(1A) receptors in the LPBN increases stimulated hypertonic NaCl and water intake, while 5-HT injections into the LPBN reduce NaCl intake and prevent the effects of serotonergic 5-HT(1A) receptor activation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2005

Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats.

The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.

Animals↗
PubMed2005

Role of nitrosyl factors in the hindlimb vasodilation elicited by baroreceptor afferent nerve stimulation.

This study determined whether electrical stimulation (ES) of the baroreceptor afferent fibers in the aortic depressor nerve (ADN) produces hindlimb vasodilation in pentobarbital-anesthetized rats via the release of nitric oxide (NO)-containing (nitrosyl) factors from NO synthase-positive lumbar sympathetic nerve terminals. ES of the ADN (1-10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and mesenteric and hindlimb vascular resistance (MR and HLR, respectively). The falls in resistance were substantially smaller in hindlimb beds in which the ipsilateral lumbar sympathetic chain had been transected 7-10 days previously. The maximal falls in MR and hindquarter vascular resistance (HQR) produced by 1- to 10-Hz ES of the ADN were unaffected by the specific inhibitor of neuronal NO synthase 7-nitroindazole (7-NI, 45 mg/kg iv). However, the total falls in HQR (mmHg.kHz(-1).s) produced by these stimuli were significantly diminished by 7-NI, whereas the total falls in MR were not affected. Four successive episodes of 10-Hz ES produced equivalent reductions in MAP, MR, and HQR. The peak changes in these parameters were not affected by 7-NI. However, the total falls in HQR progressively diminished with each successive stimulus, whereas the total falls in MR remained unchanged. These results provide evidence that the hindlimb vasodilation produced by ES of baroreceptor afferents within the ADN may involve the activation of postganglionic lumbar sympathetic vasodilator fibers, which release newly synthesized and preformed nitrosyl factors.

Afferent Pathways↗
PubMed2005

The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia.

BACKGROUND: Depression has a complex bidirectional association with heart disease. Previously we have shown notable cardiovascular changes in the chronic mild stress (CMS) rodent model of depression. Here we investigated the effects of a serotonin-specific reuptake inhibitor on a behavioral index of depression (anhedonia) and cardiac function in rats exposed to CMS. METHODS: Male Sprague-Dawley rats were exposed to either 4 weeks of control conditions or CMS, consisting of unpredictable periods of mild stressors, while being treated concurrently with 4 weeks of daily fluoxetine (10 mg/kg, sc) or vehicle. RESULTS: Chronic fluoxetine treatment prevented anhedonia in rats exposed to CMS, versus the CMS group treated with vehicle. However, treatment with fluoxetine in the CMS group only partially prevented specific cardiovascular changes associated with CMS, including elevated resting heart rate (HR), exaggerated pressor and HR responses to air jet stress, reduced cardiac output and stroke volume, and HR exaggerated responses to beta-adrenergic receptor blockade. CONCLUSIONS: These findings provide evidence that 4 weeks of fluoxetine treatment can prevent behavioral responses and can partially prevent cardiovascular changes associated with CMS, providing insight into the role of serotonin in the link between depression and cardiovascular dysfunction.

Animals↗
PubMed2005

Water intake during the development of renal hypertension (2K-1C) in mice.

For both practical and methodological reasons, mice have been the most widely employed species for development of transgenic and gene knockin and knockout animals. However, basic behavioral and physiology control and regulatory mechanisms in mice are not well characterized. To broaden our understanding of the processes maintaining body fluid and blood pressure homeostasis in the mouse, the objectives of this study were to evaluate voluntary water, and sodium intakes during the development of renal hypertension and to examine the relationship between hypertension and the quantities of water and salt ingested. In male, C57BL/6J mice, two-kidney, one-clip renal hypertension (2K-1C) was induced, and water and 1.8% NaCl intakes were monitored for 2 weeks. At the end of this period, all animals received arterial catheters for direct recording of blood pressure. The mice that received renal artery clips were sorted into hypertensive (152+/-4 mm Hg) and normotensive (122+/-2 mm Hg) groups and were compared to control (117+/-4 mm Hg) animals that underwent a sham renal clipping procedure. Hypertensive 2K-1C animals had significantly elevated water intake compared to control animals. On most of the postsurgical days, the normotensive 2K-1C animals did not display increased water intake in comparison to the control group. No significant effect was detected for 1.8% saline intake between any of the pairs of groups. In summary, the reduction of blood flow to a single kidney in the 2K-1C model of renal hypertension induces high blood pressure accompanied by sustained hyperdipsia in the mouse.

Analysis of Variance↗
PubMed2005

Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia.

A bidirectional relationship exists between depression and cardiovascular disease. Patients with major depression are more likely to develop cardiac events, and patients with myocardial infarction and heart failure are more likely to develop depression. A feature common to both clinical syndromes is activation of proinflammatory cytokines and stress hormones, including the hypothalamic-pituitary-adrenal axis and the renin-angiotensin-aldosterone system. In the present study we examined the hypothesis that exposure to chronic mild stress (CMS), an experimental model of depression that induces anhedonia in rats, is sufficient to activate the production of proinflammatory cytokines and stress hormones that are detrimental to the heart and vascular system. Four weeks of exposure of male, Sprague-Dawley rats to mild unpredictable environmental stressors resulted in anhedonia which was operationally defined as a reduction in sucrose intake without a concomitant effect on water intake. Humoral assays indicated increased plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), plasma renin activity, aldosterone, and corticosterone in the CMS exposed rats. Tissue TNF-alpha and IL-1beta were increased in the hypothalamus, and TNF-alpha was increased in the pituitary gland. These humoral responses to CMS, associated with anhedonia as an index of depression in the rat, are likely to be associated with neurohumoral mechanisms that may contribute to adverse cardiac events. The findings provide a basis for examining more directly the interactions among the central, endocrine, and immune systems in depression associated with heart disease.

Aldosterone↗