UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Left ventricular hypertrophy (LVH) is associated with reinduction of the fetal program of gene expression. It is unclear whether this pattern of cardiac gene expression changes with the development of left ventricular decompensation and failure. To answer these questions, we quantified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascending aortic banding. Clinical and hemodynamic assessment identified two distinct groups of animals 20 weeks after aortic banding. The first group (20-week nonfailed LVH) demonstrated substantial LVH but no depression in systolic developed pressure per gram left ventricular weight compared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a marked diminution in left ventricular developed pressure per gram. Assessment of the levels of mRNA encoding a panel of cardiac proteins demonstrated a greater than twofold increase in beta-myosin heavy chain mRNA and an approximately sixfold increase in atrial natriuretic factor mRNA in left ventricular myocardium of all three groups (8-week LVH, 20-week nonfailed LVH, 20-week failed LVH) when compared with appropriate age-matched control groups. In contrast, Ca(2+)-ATPase mRNA levels were decreased by 50% only in the left ventricular myocardium of animals with both clinical signs and hemodynamic indexes consistent with cardiac decompensation (20-week failed LVH). These results suggest that in rats with ascending aortic banding the hypertrophic phenotype is associated with a selective reinduction of the fetal gene program, which persists even after the development of left ventricular failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. 850 29

Nitric oxide (NO), a diffusible and unstable gas, has been implicated in inter- and intra-cellular communication in the nervous system. NO also plays a role in neural development, plasticity and alterations of synaptic function such as long-term potentiation and long-term depression (Gally et al.: Proc NY Acad Sci, 87: 354-355, 1990; Zhuo et al.: Science 260:1946-1950, 1993; Schuman and Madison.: Science 254:1503-1506, 1991; Bruhwyler et al.: Neurosci Biobehav Rev 17:373-384, 1993) some of which likely involve growth and remodelling of neurites. Some actions of NO are mediated directly by protein modification (e.g., nitrosylation) and others by activation of soluble guanylyl cyclase (soluble GC), which increases intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP). NO is synthesized by the enzyme nitric oxide synthase (NOS), which is induced by treatment of CNS neurons (Holtzman et al.: Neurobiol Disease 1:51-60, 1994) or pheochromocytoma PC12 cells (Hirsch et al.: Curr Biol 3:749-754, 1993) with NGF. NO has been proposed to mediate some of the effects of NGF on PC12 cells by inhibiting cell division (Peunova and Enikolopov: Nature 374:68-73, 1995). In addition, NO can substitute for NGF by delaying the death of trophic factor-deprived PC12 cells through a mechanism that does not involve a cytostatic action (Farinelli et al.: J Neurosci 16:2325-2334, 1996). We investigated whether NO stimulated neurite outgrowth from hippocampal neurons and PC12 cells. Primary cultures of E17 mouse hippocampal neurons co-cultured with neopallial astrocytes were exposed to the NO donors sodium nitrite (100 microM) or sodium nitroprusside (100 nM). After 48 hr, NO donor-treated cultures contained a greater proportion of cells bearing neurites and neurites that were much longer than those found in control cultures. In cultures of PC12 cells, NO donors also enhanced the neuritogenic effects of NGF. The proportion of PC12 cells with neurites 48 hr after exposure to NO donors sodium nitrite (100 microM-10mM) or sodium nitroprusside (100 nM-1 micro M) plus 2.5S nerve growth factor (NGF) was approximately twice the proportion of cells with neurites in sister cultures grown in NGF alone. Neither of the NO donors elicited neurites from the PC12 cells in the absence of NGF. The effects of the NO donors were likely mediated by release of NO since their effects were antagonized by addition of hemoglobin, which avidly binds NO, to the culture medium. The enhancement by NO of NGF-mediated neurite outgrowth in PC12 cells appeared to occur through a cGMP-dependent mechanism. The NO donors stimulated a prompt increase in intracellular cGMP in PC12 cells. Moreover their action was mimicked by addition of the membrane-permeant cGMP analogs 8-Bromo-cGMP (8-Br-cGMP) and para (chlorophenylthio)-cGMP (pCPT-cGMP) to the culture medium and by atrial natriuretic factor which stimulates particulate guanylyl cyclase. The neuritogenic activity of the NO donors was inhibited by LY83583 and methylene blue, inhibitors of guanylyl cyclase. These data imply that NO may act alone or with other growth factors to regulate synapse formation and maintenance by stimulating neurite outgrowth.
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PMID:Nitric oxide donors enhance neurotrophin-induced neurite outgrowth through a cGMP-dependent mechanism. 905 36

We have previously established the existence of atrial natriuretic factor (ANF) gene expression within the renal parenchyma. Neither the role nor the regulation of this extracardiac source of ANF is clearly defined. To determine whether renal ANF gene expression, similar to cardiac expression, is linked to the activity of the renin-angiotensin system (RAS), we compared renal ANF gene expression in rats after suprarenal aortic banding, a hypertension model associated with activation of RAS, and in the deoxycorticosterone acetate (DOCA)-salt model, which is characterized by depression of RAS. Renal ANF mRNA was measured with a quantitative competitive reverse transcription polymerase chain reaction method. DOCA-salt hypertension significantly reduced the expression of renal ANF. In contrast, aortic banding significantly increased renal ANF expression. In both cases, ANF gene expression in the heart increased. Ramipril treatment at 10 micrograms/kg of aortic-banded rats, a treatment that specifically affects local RAS but maintains hypertension, normalized renal ANF mRNA levels. Altogether, these results suggest that renal ANF gene expression is modulated by local RAS and is independent of circulating RAS and hypertension per se. The marked decrease of renal ANF mRNA in DOCA-salt hypertension suggests a pathogenic role for renal ANF gene downregulation by decreasing the sodium excretory mechanism mediated by the local expression of ANF acting on receptors found in the inner medullary collecting ducts. In aortic banding, renal ANF gene expression upregulation suggests a local compensatory function consistent with the consensus role of natriuretic peptides in the modulation of RAS, thus ameliorating the sodium-retaining effects of renal underperfusion.
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PMID:Variable renal atrial natriuretic factor gene expression in hypertension. 1037 13

Adenosine protects the ischemic myocardium by coronary vasodilation and the depression of heart rate and contractility, improving myocardial energy balance. Adenosine effects on the myocardium are mediated predominantly by the type A1 receptors. Atrial natriuretic peptide (ANP), a vasodilator and regulator of blood volume, is secreted from either atrial or ventricular myocytes in response to cellular distention. In vivo, adenosine infusion has been shown to induce a rapid increase in plasma ANP, independent of blood pressure. We examined the possibility that adenosine enhances ANP-gene expression in cardiac myocytes. Administration of adenosine (10 microM) to cultured neonatal rat cardiomyocytes led to a 1.7-fold increase (p = 0.014, n = 9) in the abundance of ANP messenger RNA (mRNA) within 30 min, as measured by Northern blot hybridization. No such increase was obtained when adenosine was coadministered with 8-cyclopentyl-1,3dipropylxanthine (CPX, 10 microM), an adenosine A1-receptor antagonist. Our results point at adenosine as regulator of ANP mRNA level in cardiac myocytes.
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PMID:Adenosine stimulates ANP expression in cultured ventricular cardiomyocytes. 1041 60

Atrial natriuretic peptide (ANP) has potent vasodilatory and natriuretic actions and may have therapeutic benefit in congestive heart failure (CHF). These benefits may be offset by a negative inotropic effect of ANP seen in isolated preparations. However, ANP's integrated effect on left ventricular (LV) contraction and relaxation, independent of loading conditions, both under normal conditions and after CHF, is not known. We studied six conscious dogs, instrumented to measure LV and left atrial pressures and to determine LV volume from three dimensions. ANP produced significant (P<.05) decreases in LV end-systolic pressure (101.2+/-11.8 versus 91.7+/-11.2 mm Hg, P<.05) in normal dogs and in dogs with CHF (93.1+/-6.4 versus 87.1+/- 4.4 mm Hg, P<.05). ANP also caused significant reductions of the slope of end-systolic pressure-end-systolic volume relation both before (7.0 +/-1.5 versus 6.3+/-1.5 mm Hg/ml) and after CHF (4.8+/-1.3 versus 4.4+/-1.2 mm Hg/ml, P<.05). Both before and after CHF, ANP slowed LV relaxation at matched end-systolic pressure. Before CHF, steady-state stroke volume and peak LV filling rate (dV/dt(max)) were reduced. However, after CHF, the fall in end-systolic pressure more than offset the load-independent LV depression, as stroke volume, the rate LV relaxation, and dV/dt(max) were increased and minimum LV pressure reduced. ANP has negative effects on LV contractility and relaxation both before and after CHF. However, after CHF, afterload reduction with ANP overcomes its negative effects, resulting in net improvement of LV ejection and relaxation. Thus, the direct cardiodepressant effects of ANP should not limit its usefulness in CHF.
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PMID:Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure. 1052 76

Atrial natriuretic peptide (ANP) and its analog, atriopeptin III (APIII), inhibit carotid body chemoreceptor nerve activity evoked by hypoxia. In the present study, we have examined the hypothesis that the inhibitory effects of ANP and APIII are mediated by cyclic GMP and protein kinase G (PKG) via the phosphorylation and/or dephosphorylation of K(+) and Ca(2+) channel proteins that are involved in regulating the response of carotid body chemosensory type I cells to low-O(2) stimuli. In freshly dissociated rabbit type I cells, we examined the effects of a PKG inhibitor, KT-5823, and an inhibitor of protein phosphatase 2A (PP2A), okadaic acid (OA), on K(+) and Ca(2+) currents. We also investigated the effects of these specific inhibitors on intracellular Ca(2+) concentration and carotid sinus nerve (CSN) activity under normoxic and hypoxic conditions. Voltage-dependent K(+) currents were depressed by hypoxia, and this effect was significantly reduced by 100 nM APIII. The effect of APIII on this current was reversed in the presence of either 1 microM KT-5823 or 100 nM OA. Likewise, these drugs retarded the depression of voltage-gated Ca(2+) currents induced by APIII. Furthermore, APIII depressed hypoxia-evoked elevations of intracellular Ca(2+), an effect that was also reversed by OA and KT-5823. Finally, CSN activity evoked by hypoxia was decreased in the presence of 100 nM APIII, and was partially restored when APIII was presented along with 100 nM OA. These results suggest that ANP initiates a cascade of events involving PKG and PP2A, which culminates in the dephosphorylation of K(+) and Ca(2+) channel proteins in the chemosensory type I cells.
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PMID:Cellular mechanisms involved in carotid body inhibition produced by atrial natriuretic peptide. 1075 32

Glucocorticoids are administered for preterm labor to improve postnatal adaptation. We assessed the effect of antenatal betamethasone (Beta) treatment on preterm newborn lamb neuroendocrine [catecholamine, arginine vasopressin (AVP)] and endocrine [triiodothyronine (T(3)), ANG II, and atrial natriuretic factor (ANF)] adaptive responses following delivery and a hypoxic challenge. Beta treatment included direct fetal injection at 0.2 (F(0.2); n = 8) or 0.5 (F(0.5); n = 7) mg/kg estimated fetal body weight or maternal injection with 0.2 (n = 8) or 0.5 mg/kg (M(0.5); n = 8). Control animals received fetal and maternal intramuscular injections of saline (n = 8). After 24 h, lambs were delivered by cesarean section, surfactant treated, and ventilated for 4 h. Relative to the control lambs, 3 h after delivery, there was a marked suppression of plasma cortisol, epinephrine, norepinephrine, and ANG II levels and elevated plasma T(3) and ANF levels, systolic blood pressure, and left ventricular contractility (dP/dt; F(0.5) and M(0.5)) values in F(0.5) and both maternal Beta-treated groups. However, Beta treatment augmented the cardiac output, cortisol, norepinephrine, AVP, and ANF responses to 20 min of hypoxia (PO(2) = 25-30 mmHg). We concluded that short-term (24 h) antenatal glucocorticoid exposure 1) alters preterm newborn postnatal blood pressure regulation in the face of marked depression of plasma cortisol, catecholamine, and ANG II levels and 2) augments the postnatal neuroendocrine and endocrine responses to a hypoxic challenge.
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PMID:Antenatal glucocorticoids alter premature newborn lamb neuroendocrine and endocrine responses to hypoxia. 1095 40

In pressure overload-induced hypertrophy, the heart increases its reliance on glucose as a fuel while decreasing fatty acid oxidation. A key regulator of this substrate switching in the hypertrophied heart is peroxisome proliferator-activated receptor alpha (PPARalpha). We tested the hypothesis that down-regulation of PPARalpha is an essential component of cardiac hypertrophy at the levels of increased mass, gene expression, and metabolism by pharmacologically reactivating PPARalpha. Pressure overload (induced by constriction of the ascending aorta for 7 days in rats) resulted in cardiac hypertrophy, increased expression of fetal genes (atrial natriuretic factor and skeletal alpha-actin), decreased expression of PPARalpha and PPARalpha-regulated genes (medium chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase 4), and caused substrate switching (measured ex vivo in the isolated working heart preparation). Treatment of rats with the specific PPARalpha agonist WY-14,643 (8 days) did not affect the trophic response or atrial natriuretic factor induction to pressure overload. However, PPARalpha activation blocked skeletal alpha-actin induction, reversed the down-regulation of measured PPARalpha-regulated genes in the hypertrophied heart, and prevented substrate switching. This PPARalpha reactivation concomitantly resulted in severe depression of cardiac power and efficiency in the hypertrophied heart (measured ex vivo). Thus, PPARalpha down-regulation is essential for the maintenance of contractile function of the hypertrophied heart.
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PMID:Reactivation of peroxisome proliferator-activated receptor alpha is associated with contractile dysfunction in hypertrophied rat heart. 1157 33

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder, and post-traumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by corticotropin-releasing hormones (CRH),corticosteroids,and their receptors, and the roles of natriuretic peptides and neuroactive steroids are described. We review the role of the HPA system in major depression, panic disorder, and post-traumatic stress disorder and its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones such as CRH, to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that nonpeptidergic ANP receptor ligands may be potentially useful in the treatment of anxiety disorders. Post-traumatic stress disorder is characterized by a peripheral hyporesponsive HPA system and elevated CRH concentrations in the CSF. This dissociation is probably related to an increased risk of this disorder. We further review recent data that describe an important role of GABA(A)-receptor modulatory,3 alpha-reduced neuroactive steroids in major depression, anxiety, and its treatment. Antidepressants are effective in both depression and anxiety disorders and have major effects on the HPA system,especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. Currently,CRH-R1 or glucocorticoid receptor antagonists and ANP receptor agonists are being studied and may provide future treatment options more closely related to the pathophysiology of these disorders.
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PMID:[The neuroendocrinology of stress and the pathophysiology and therapy of depression and anxiety]. 1262 45

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder and posttraumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by CRH, corticosteroids and their receptors as well as the role of natriuretic peptides and neuroactive steroids are described. Examplarily, we review the role of the HPA system in major depression, panic disorder and posttraumatic stress disorder as well as its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones, like CRH to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that non-peptidergic ANP receptor ligands may be of potential use in the treatment of anxiety disorders. Recent data further suggest a role of 3alpha-reduced neuroactive steroids in major depression, panic attacks and panic disorder. Posttraumatic stress disorder is characterized by a peripheral hyporesponsive HPA-system and elevated CRH concentrations in CSF. This dissociation is probably related to an increased risk for this disorder. Antidepressants are effective both in depression and anxiety disorders and have major effects on the HPA-system, especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA-system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. CRH-R1 or glucorticoid receptor antagonists and ANP receptor agonists are currently being studied and may provide future treatment options more closely related to the pathophysiology of the disorders.
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PMID:Stress responsive neurohormones in depression and anxiety. 1467 81

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