Long-term high-fat diet-induced obesity decreases the cardiac leptin receptor without apparent lipotoxicity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats

Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5 mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4 ma/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo 111). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p < 0.01). Lycopene levels (mean +/- S.D. nmol/kg) in saponified hearts were similar between L (47.43 +/- 11.78) and DL (49.85 +/- 16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage. (c) 2007 Elsevier B.V. All rights reserved.

Cardiac hemangioma of the right atrium

Primary cardiac tumors are rare, with an incidence range between 0.001% and 0.030% at autopsy. Recent technical advances have facilitated diagnosis and surgical treatment of such lesions. Patients with a resectable tumor usually have a good prognosis, but patients with an unresectable tumor may have a poor prognosis. This report shows a case of right atrial hemangioma growing like an extracardiac mass, with cardiac tamponade the only clinical presentation.

Commissural nucleus of the solitary tract is important for cardiovascular responses to caudal pressor area activation

The nucleus of the solitary tract (NTS) is the site of the first synapse of cardiovascular afferent fibers in the central nervous system. Important mechanisms for cardiovascular regulation are also present in the caudal pressor area (CPA) localized at the caudal end of the ventrolateral medulla. In the present study we sought to investigate the role of the commissural subnucleus of the NTS (commNTS) on pressor and tachycardic responses induced by L-glutamate injected into the CPA. Male Holtzman rats (n=8 rats/group) anesthetized with urethane (1.2 g/kg of body weight, iv) received injections of the GABAA receptor agonist muscimol into the commNTS. Unilateral injection of L-glutamate (10 nmol/ 100 nL) into the CPA increased mean arterial pressure (MAP, 31 4 mm Hg, vs. saline: 3 +/- 2 mm Hg) and heart rate (HR, 44 8 bpm, vs. saline: 10 7 bpm). inhibition of commNTS neurons with muscimol (120 pmol/60 nL) abolished the increase in MAP (9 4 mm Hg) and HR (17 7 bpm) produced by L-glutamate into the CPA. The present results suggest that the pressor and tachycardic responses to CPA activation are dependent on commNTS mechanisms.

Sympathetic mediation of salivation induced by intracerebroventricular pilocarpine in rats

Central cholinergic activation by pilocarpine induces salivation dependent on the integrity of forebrain areas. The present work investigates the autonomic mediation of this salivation. Pilocarpine (500 nmol/rat) was injected into the lateral ventricle (LV) of tribromoethanol-anesthetized adult male rats. Preweighed cotton balls were inserted into the oral cavity and weighed again 7 min later. ol-adrenoceptor antagonists (3-50 mu mol/kg) prazosin (alpha(1)), yohimbine (alpha(2)) or propranolol (beta) injected intraperitoneally (i.p.) produced, 80%, 20% and 0% inhibition respectively of the LV pilocarpine-induced salivation. Intracerebroventricular injections (160 nmol) of the antagonists did not alter the effects of pilocarpine injected into the LV. Bilateral section of chorda tympani nerve or bilateral sympathetic cervical ganglionectomy produced 0% and 40% inhibition of pilocarpine-induced salivation, respectively. Ganglionectomy did not alter salivation induced by i.p, injection of pilocarpine (4 mu mol/kg). The results indicate that there is a large sympathetic contribution to the salivation induced by central cholinergic activation. (C) 1999 Elsevier B.V. B.V. All rights reserved.

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t) SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e. g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EHrats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.

Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Chemosensory control by commissural nucleus of the solitary tract in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diet-induced obesity causes metabolic, endocrine and cardiac alterations in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiac remodeling in a rat model of diet-induced obesity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)