Insulin resistance plays an intricate role in the development of cardiovascular diseases, hypertension is associated with insulin-resistant states such as diabetes and obesity. However, the underlying mechanism to explain the associations between hypertension and insulin resistance is unknown. The insulin exerts various biological effects in different type of cells. Clinical studies have reported that insulin has been shown to stimulate the protein kinase Akt via activation of PI3K in endothelial cells. Furthermore, insulin stimulated production of nitric oxide (NO) is inhibited by wortmannin in human umbilical vein endothelial cells (HUVECs). We also reported previously that NO contributes to the regulation of blood pressure in central nervous system. The aim of this study was to elucidate the potential mechanisms linking hypertension with insulin resistance and whether insulin signaling may involved in cardiovascular regulation in rat NTS neurons, we investigated the cardiovascular effects of insulin in the nucleus tractus solitarii (NTS) of urethane-anesthetized male spontaneous hypertensive rat (SHR) and normotensive Wistar-kyoto rats (WKY). Unilateral microinjection of insulin (100 IU/ml) into the NTS produced prominent depressor and bradycardic effects in 8/16 week-old WKY. However, no significant cardiovascular effects were found in adult SHR (16 week-old) after insulin injection. Furthermore, young SHR (8 week-old) with normal blood pressure showed depressor and bradycardic effects after insulin injection. Pretreatment with PI3K inhibitor LY294002 and NO synthase inhibitor L-NAME into the NTS attenuated the cardiovascular response evoked by insulin in WKY and young SHR but not in adult SHR. Furthermore, insulin induced Akt phosphorylation in-situ in WKY and SHR rats. Thus, these results indicated that insulin-PI3K-Akt-NOS sensitive mechanisms were involved in WKY and young SHR (normotensive) but not in adult SHR (hypertensive). The results also suggested the possible defective insulin signaling may resulted in the development of hypertension in adult SHR.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009. / Härtill 3 uppsatser.

Zugl.: Giessen, Universiẗat, Diss., 2009.

The hormone relaxin regulates the release of the magnocellular hormones, oxytocin and vasopressin, from the central nervous system. Studies have yet to determine whether relaxin regulates magnocellular hormone release through the circumventricular organs alone, or whether relaxin can act on the brain regions containing the magnocellular neurons as well. The paraventricular nucleus of the hypothalamus was isolated from other brain regions and maintained in vitro, in order evaluate the effects of the relaxin and relaxin-3 on the somatodendritic release of oxytocin and vasopressin. At 50 nM concentrations, relaxin induced oxytocin release, while relaxin-3 inhibited oxytocin release. Neither relaxin nor relaxin-3 had an effect on the vasopressin release, however the RXFP3 specific agonist, R3/I5, induced vasopressin release. The effect of the relaxin peptides on the electrical activity of neurons in the paraventricular nucleus was also evaluated. Relaxin depolarized magnocellular neurons while relaxin-3 hyperpolarized the neurons. Relaxin and relaxin-3 appear to have differential effects on the magnocellular neurons of the paraventricular nucleus.

Psychological stressors such as social stress and bullying are prevalent in today’s society. Disorders such as PTSD, depression and social anxiety disorder can be either caused or exacerbated by social stress and treatment options are not always effective in providing relief for these disorders. Our laboratory studies a form of social stress termed conditioned defeat, whereby a defeated Syrian hamster no longer displays species-typical territorial aggression but instead is submissive and defensive toward an intruder in its own cage. We hypothesized that the nucleus accumbens is a necessary component of the circuit mediating the acquisition and expression of conditioned defeat and that dopamine is necessary within the nucleus accumbens for inducing memory processes as well as expression of behavioral responses to stressful situations. We also hypothesized that defeat activates dopaminergic and/or nondopaminergic neurons in the ventral tegmental area (VTA) and that dopamine released by neurons projecting from the VTA to the nucleus accumbens and basolateral amygdala (BLA) increases neuronal activation of these structures during defeat. We found that dopamine, but not GABA, modulates memory of social defeat within the nucleus accumbens. However, GABA does affect the expression of behavioral responses to social defeat. Defeat also increased Fos activation of non-dopaminergic neurons, but it did not increase activation of dopaminergic neurons. Baclofen infusion into the VTA prior to defeat, which was hypothesized to specifically inhibit dopaminergic neurons, did not affect Fos activation within the nucleus accumbens and the basolateral amygdala. These experiments determined that dopamine does modulate memory of social defeat within the nucleus accumbens, but it is currently unclear what the source of this dopamine is. Future experiments are planned to determine this source of dopamine that could be a target of treatment for disorders that are caused or exacerbated by social stress.

Proefschift Universiteit van Amsterdam. / Met een samenvatting in het Nederlands.

Zugl.: Berlin, Charité, University-Med., Diss., 2006.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 3 uppsatser.

Thesis (Ph.D.)--University of Melbourne, Dept. of Otolaryngology, 2005. / Typescript. Author's name on spine: B.Y. Cahyono. Includes bibliographical references (p. 185-220).

Thesis (Ph. D.)--University of Missouri--Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 168-184). Also available on the Internet.