Cholestasis: The Close Relationship between Bile Acids and Coenzyme Q10

Cholestasis is defined as the impairment in formation or excretion of bile from the liver to the intestine. It may result from defects in intrahepatic production of bile, impairment of hepatic transmembrane transporters, or mechanical obstruction to bile flow. In cholestasis, hepatocytes are exposed to high levels of bile acids, particularly those bearing hydrophobic properties. The increase in bile acids induces oxidative stress, leading to an imbalance in the prooxidant:antioxidant ratio which determines the final cellular redox status. This chapter will focus on the close relationship between bile acids and the most powerful endogenous antioxidant, coenzyme Q10 in cholestasis, and the eventual alternative therapeutic option of CoQ10 supplementation to current traditional therapies

The olfactory bulb: an ignored brain structure in the regulation of cardiovascular activity

Numerous studies have addressed the participation of the central nervous system in the physiological regulation of blood pressure and in the development and/or maintenance of hypertension. The central nervous system plays a key role in the short-term regulation of blood pressure although recent investigations also support its participation in the long-term modulation. Diverse brain regions and areas like the rostral ventrolateral medulla, the nucleus of the solitary tract, the locus coeruleus, amygdala and hypothalamus are intimately involved in the control of cardiovascular activity. Nevertheless, little is known about the role of the olfactory bulb. This mini review summarizes current knowledge regarding the participation of this telencephalic region in the regulation of cardiovascular activity in physiological and pathophysiological conditions.Numerosos estudios han abordado la participación del sistema nervioso central en la regulación fisiológica de la presión arterial y en el desarrollo y / o mantenimiento de la hipertensión arterial. El sistema nervioso central juega un papel clave en la regulación a corto plazo de la presión arterial, aunque investigaciones recientes apoyan su participación en la modulación a largo plazo. Diversas regiones y áreas del cerebro como la médula ventrolateral rostral, el núcleo del tracto solitario, el locus coeruleus, la amígdala y el hipotálamo están íntimamente involucradas en el control de la actividad cardiovascular. Sin embargo, poco se conoce acerca del papel del bulbo olfatorio. Esta breve revisión resume el conocimiento actual en la participación de esta región telencefálica en la regulación de la actividad cardiovascular en condiciones fisiológicas y fisiopatológicas.Sociedad Argentina de Fisiologí

EL RETÍCULO ENDOPLÁSMICO TAMBIÉN SE ESTRESA. IMPORTANCIA EN LA PATOGÉNESIS DE LA PANCREATITIS AGUDA

La pancreatitis aguda continúa siendo preocupante debido a su curso clínico incierto, pero también a que no se dispone de una terapéutica específica. El estrés del retículo endoplásmico está involucrado en etapas tempranas de su desarrollo. La modulación de las vías celulares que se activan para revertirlo podría constituir la clave en la búsqueda de futuros blancos terapéuticos, no solo para esta patología sino además para otras

Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors

Increasing evidence supports the role of atrial natriuretic factor (ANF) in the modulation of gastrointestinal physiology. The effect of ANF on exocrine pancreatic secretion and the possible receptors and pathways involved were studied in vivo. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into the duodenum. ANF dose-dependently increased pancreatic secretion of fluid and proteins and enhanced secretin and CCK-evoked response. ANF decreased chloride secretion and increased the pH of the pancreatic juice. Neither cholinergic nor adrenergic blockade affected ANF-stimulated pancreatic secretion. Furthermore, ANF response was not mediated by the release of nitric oxide. ANF-evoked protein secretion was not inhibited by truncal vagotomy, atropine, or Nω-nitro-L-arginine methyl ester administration. The selective natriuretic peptide receptor-C (NPR-C) receptor agonist cANP-(4-23) mimicked ANF response in a dose-dependent fashion. When the intracellular signaling coupled to NPR-C receptors was investigated in isolated pancreatic acini, results showed that ANF did not modify basal or forskolin-evoked cAMP formation, but it dose-dependently enhanced phosphoinositide hydrolysis, which was blocked by the selective PLC inhibitor U-73122. ANF stimulated exocrine pancreatic secretion in the rat, and its effect was not mediated by nitric oxide or parasympathetic or sympathetic activity. Furthermore, CCK and secretin appear not to be involved in ANF response. Present findings support that ANF exerts a stimulatory effect on pancreatic exocrine secretion mediated by NPR-C receptors coupled to the phosphoinositide pathway.Fil: Sabbatini, María E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Villagra, Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Vatta, Marcelo Sergio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Fernandez, Belisario Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Bianciotti, Liliana Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats

Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ETA) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ETA blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ETA blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ETA are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension