ABSTRACT
The cardiovascular effects elicited by the ethanolic extract obtained from the roots of Erythroxylum pungens O.E. Schulz, Erythroxylaceae (EEEP) and the vasorelaxant effect induced by its main tropane alkaloid (pungencine) were investigated. In normotensive rats, administration of EEEP (1, 10, 30 and 60 mg/kg i.v., randomly) produced dose-dependent hypotension (-2±1, -7±0.5 -17.6±1, -24±1 Δ mmHg, n=5) followed by tachycardia (3±0.5, 7±2, 7.1±1, 10±5 Δ bpm, n=5). In intact phenylephrine (Phe, 10 µM)-pre-contracted rings, EEEP (0.01-500 µg/mL) induced concentration-dependent vasorelaxation (EC50 13.7±5.5 µg/mL, Maximal Response= 92±2.6%), and this effect was unchanged after the removal of the vascular endothelium (EC50 27.2±4.7 µg/ml, Maximal Response= 88.3±3.3 %). In KCl (80 mM)-pre-contracted-endothelium-denuded rings, EEEP elicited concentration-dependent relaxation (EC50= 128.2±11.2 µg/mL, Maximal Response 76.8±3.4%). Vasorelaxation has also been achieved with tonic contractions evoked by the L-type Ca2+ channel agonist Bay K 8644 (EC50 80.2±9.1 µg/mL, Maximal Response 86.3±8.3%). In addition, in a depolarizing medium, EEEP inhibited CaCl2 (30-500 µg/mL) induced contractions and caused a concentration-dependent rightward shift of the relaxation curves. Lastly, the tropane alkaloid pungencine caused vasorelaxation in mesenteric arteries resembling to the EEEP responses. These results suggests that EEEP induces hypotension and vasorelaxation, at least in part, due to the reduction in [Ca2+]i in vascular smooth muscle cells.
ABSTRACT
OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2 percent for the first week, 5 percent for the second week and 10 percent for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9) or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group). CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.
Subject(s)
Animals , Male , Mice , Alcoholic Beverages , Anxiety/psychology , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Saccharum/chemistry , Alanine Transaminase/blood , Anxiety/chemically induced , Aspartate Aminotransferases/blood , Liver/drug effects , Liver/growth & development , Liver/pathology , Time FactorsABSTRACT
RESUMO: Essa revisão tem como objetivo apresentar a experiência do nosso laboratório, acumulada ao longo dos últimos anos no estudo da neurotransmissão do componente simpatoexcitatório do quimiorreflexo no núcleo do trato solitário (NTS) de ratos. Essa abordagem experimental tem sido utilizada como um modelo para o melhor entendimento dos mecanismos neuroquímicos envolvidos na geração e modulação da atividade simpática, a qual tem importantes repercussões para o sistema cardiovascular tanto em condições fisiológicas quanto em condições fisiopatológicas como a hipertensão arterial. O foco específico dessa revisão está centrado na neurotransmissão do componente simpato-excitatório do quimiorreflexo no núcleo do trato solitário (NTS) e apresentamos vários métodos e abordagens experimentais que estão sendo utilizados com vistas ao melhor entendimento desse complexo sistema de neurotransmissão. Com essa combinação de métodos, que vão desde um neurônio do NTS até o rato acordado e com livre movimentação, queremos ilustrar as múltiplas possibilidades de abordagens experimentais contemporâneas, as quais estão nos proporcienando as condições materiais para estender os horizontes dessa importante área do conhecimento.