RESUMO
The recreational use of 3,4-methylenedioxymethamphetamine (MDMA) has increased as have the number of clinical reports linking MDMA use with cardiovascular toxicity. Nonetheless, the cardiovascular and sympathetic nerve responses elicited by MDMA have not been well characterized. The purpose of this study was to characterize the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve responses elicited by the acute administration of MDMA and to determine whether neurotoxic doses of MDMA change cardiovascular and/or cardiovascular reflex function. In conscious rats, MDMA or d-amphetamine elicited similar dose-dependent increases in MAP. MDMA elicited significant bradycardia at doses above 1.0 mg/kg. Pretreatment with phentolamine significantly reduced the duration but not the magnitude of the pressor response elicited by MDMA. In pentobarbital-anesthetized rats, MDMA (0.1 mg/kg) increased renal sympathetic nerve activity (RSNA; 33 +/- 10%), while larger doses significantly decreased RSNA (-91 +/- 3%, max). Neurotoxic doses of MDMA (20 mg/kg, s.c., b.i.d. for 4 days) significantly enhanced the bradycardic component of the Bezold-Jarisch reflex elicited by i.v. serotonin when tested either 2 days or 2 weeks after the last neurotoxic treatment. However, neurotoxic treatment did not significantly affect baroreceptor reflex function. These results indicate that the acute administration of MDMA and d-amphetamine produce similar cardiovascular and sympathetic responses. Neurotoxic doses of MDMA can also significantly alter cardiovascular reflex function. These findings raise the possibility that MDMA may have the potential to produce cardiovascular and/or cardiac toxicity similar to that elicited by other amphetamine analogs.
Assuntos
Hemodinâmica/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Reflexo/efeitos dos fármacos , Serotoninérgicos/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Anfetamina/farmacologia , Anestesia , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Serotoninérgicos/toxicidadeRESUMO
Two new loci, irrB and irrI, have been identified in Deinococcus radiodurans. Inactivation of either locus results in a partial loss of resistance to ionizing radiation. The magnitude of this loss is locus specific and differentially affected by inactivation of the uvrA gene product. An irrB uvrA double mutant is more sensitive to ionizing radiation than is an irrB mutant. In contrast, the irrI uvrA double mutant and the irrI mutant are equally sensitive to ionizing radiation. The irrB and irrI mutations also reduce D. radiodurans resistance to UV radiation, this effect being most pronounced in uvrA+ backgrounds. Subclones of each gene have been isolated, and the loci have been mapped relative to each other. The irrB and irrI genes are separated by approximately 20 kb of intervening sequence that encodes the uvrA and pol genes.