RESUMEN
Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.
Asunto(s)
Aorta , GMP Cíclico , Emulsiones , Labetalol , Óxido Nítrico Sintasa de Tipo III , Vasodilatación , Animales , Vasodilatación/efectos de los fármacos , Ratas , Aorta/efectos de los fármacos , Aorta/metabolismo , Labetalol/farmacología , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , GMP Cíclico/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Ratas Sprague-Dawley , Humanos , Lípidos , Fosforilación/efectos de los fármacos , Calcio/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismoRESUMEN
Proline (Pro) metabolism in plants is involved in various cellular processes mediated during abiotic stress. However, the Pro-regulatory mechanisms are unclear. We used a suppressor mutation technique to isolate novel genes involved in the regulation of Pro metabolism in Arabidopsis. Using atrzf1 as a parental plant for T-DNA tagging mutagenesis, we identified a suppressor mutant, termed proline content alterative 21 (pca21), that displayed reduced Pro contents compared with the atrzf1 under osmotic stress conditions. Genomic Thermal Asymmetric Interlaced (TAIL)-PCR revealed pca21 harbored an inserted T-DNA in the region of At2g36620 that encodes Ribosomal Protein L24A. In general, the pca21 mutant partially suppressed the insensitivity of atrzf1 to osmotic stress and abscisic acid during seed germination and early seedling stage. Additionally, the pca21 mutant had increased MDA content and lower expression of several Pro biosynthesis-related genes than the atrzf1 mutant during drought condition. These results suggest that pca21 acts as partial suppressor of atrzf1 in the osmotic stress response through the Pro-mediated pathway.
Asunto(s)
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Sequías , Prolina/metabolismo , Proteínas Ribosómicas/metabolismo , Estrés Fisiológico/fisiología , Regulación hacia Abajo/fisiología , Mutación/genética , Ósmosis/fisiología , Presión OsmóticaRESUMEN
Left ventricular free wall rupture (LVFWR) is a serious complication of myocardial infarction. It presents with a very high mortality rate and can be rescued by accurate diagnosis and emergency surgery. LVFWR can occur with sudden overt clinical symptoms or present insidiously. This report highlights the case of a man with no prior history of coronary artery disease, who presented with LVFWR and pericardial effusion that evolved to severe bacterial pericarditis.