adrenomedullin and Anxiety-Disorders

To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension.. Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients.. There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21 ± 88.81% versus 56.01 ± 7.85%, p>0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05 ± 9.42 versus 123.57 ± 7.01 g/m(2), p=0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97 ± 5.48 versus 18.32 ± 6.97 ng/L, p=0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r=0.734, p<0.05) and control group (r=0.592, p<0.05).. Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.

Topics: Adrenomedullin; Adult; Aged; Anxiety Disorders; Case-Control Studies; Essential Hypertension; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Ultrasonography; Ventricular Function, Left; Young Adult

Whereas severe hypoxia is known to contribute to neuronal death and to lead to neurological disturbances, mild hypoxia can also induce beneficial effects through endogenous adaptive responses. The aim of this study was to investigate the effects of mild hypoxia (8% O(2)) on cognitive and emotional behavior in the adult mouse. To this end, mice were submitted to repeated mild hypoxia exposure or normoxia during 6 weeks and underwent behavioral testing during the last 3 weeks. Hypoxia decreased anxiety-like behavior in the light/dark transition test, enhanced, albeit modestly, non-spatial recognition memory, but did not alter spontaneous locomotor activity, nor spatial learning. On additional mice, whole brain adrenomedullin mRNA expression was found to be increased at D1, D25 and D41 after hypoxia initiation and vascular endothelial growth factor (VEGF) mRNA expression was increased at only on D41. This work shows that repeated mild hypoxic exposure decreases anxiety-related behavior and points out hypoxia inducible factor-1 (HIF-1) target genes, particularly adrenomedullin, as potential mediator candidate.

Topics: Adrenomedullin; Analysis of Variance; Animals; Anxiety Disorders; Brain; Gene Expression Regulation; Hypoxia; Hypoxia-Inducible Factor 1; Locomotion; Male; Maze Learning; Mice; Recognition, Psychology; RNA, Messenger; Time Factors; Vascular Endothelial Growth Factor A

The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous system (CNS) and several functions have been suggested for brain AM. Until now, a formal confirmation of these actions using genetic models has been elusive since the systemic adm knockout results in embryo lethality. We have built a conditional knockout mouse model using the Cre/loxP approach. When crossed with transgenic mice expressing the Cre recombinase under the tubulin Talpha-1 promoter, we obtained animals with no AM expression in the CNS but normal levels in other organs. These animals lead normal lives and do not present any gross morphological defect. Specific areas of the brain of animals lacking CNS AM contain hyperpolymerized tubulin, a consequence of AM downregulation. Behavioral analysis shows that mice with no AM in their brain have impaired motor coordination and are hyperactive and overanxious when compared to their wild-type littermates. Treatment with methylphenidate, haloperidol, and diazepam did not show differences between genotypes. Circulating levels of adrenocorticotropic hormone and corticosterone were similar in knockout and wild-type mice. Animals with no brain AM were less resistant to hypobaric hypoxia than wild-type mice, demonstrating the neuroprotective function of AM in the CNS. In conclusion, AM exerts a beneficial action in the brain by maintaining homeostasis both under normal and stress conditions.

Topics: Adrenomedullin; Animals; Anxiety Disorders; Brain Chemistry; Genotype; Homeostasis; Hypoxia; Mental Disorders; Mice; Mice, Knockout; Motor Skills Disorders; Survival Rate; Tubulin