ABSTRACT
OBJECTIVE: Both atrial fibrillation (AF) and heart failure (HF) are increasingly prevalent and related to high hospitalization rate and mortality. AF is a cause as well as a consequence of HF, with complicated interactions resulting in impairment of cardiac systolic and diastolic function. Conversely, the complex structural and neurohormonal alterations in HF contribute to the occurrence and development of AF. However, the molecular mechanism remains unclear. This study aims to explore the effect of Exchange-protein activated by cAMP 1 (EPAC1) on AF in isoproterenol (ISO)-induced HF and the potential molecular mechanism. MATERIALS AND METHODS: Mice and cultured isolated adult cardiomyocytes were treated with ISO and or not EPAC1 inhibitor CE3F4. Programmed electrical stimulation (PES) was performed to induce AF. EPAC1 expression was determined by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and Western blot. Cellular electrophysiology was examined by whole cell patch clamp. RESULTS: Both mRNA and protein levels of EPAC1 were upregulated in HF mice. ISO increased the AF susceptibility, and the negative effect was deteriorated by CE3F4. ISO mediated high AF susceptibility of HF via prolonging action potential and exciting L-type calcium channel (LTCC). These could also be reversed by CE3F4 treatment. CONCLUSIONS: EPAC1 increased the AF susceptibility in ISO-induced HF mouse model via alternating LTCC.
Subject(s)
Atrial Fibrillation/diagnosis , Calcium Channels, L-Type/metabolism , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Heart Failure/complications , Isoproterenol/adverse effects , Animals , Atrial Fibrillation/etiology , Atrial Fibrillation/genetics , Atrial Fibrillation/metabolism , Cells, Cultured , Disease Models, Animal , Electrophysiologic Techniques, Cardiac , Heart Failure/chemically induced , Heart Failure/genetics , Heart Failure/metabolism , Male , Mice , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Quinolines/pharmacology , Up-Regulation/drug effectsABSTRACT
A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.
ABSTRACT
In the present study, the effects of lycium barbarum polysaccharide (LBP) on endothelial function in the two-kidney, one clip model of hypertension were observed. The results showed that the increase of blood pressure in hypertension rats (HR) could be prevented significantly by treatment with 10% LBP. In isolated aortic rings of LBP-treated rats, the contraction of phenylephrine (PE) was reduced as compared with HR rats. Removal of the endothelium abolished the difference of PE-induced vasoconstriction among groups. In vitro incubation of aortic rings from LBP-treated rats with methyl blue (MB) or N-nitro-L-arginine methyl ester (L-NAME) increased the magnitude of PE-induced contraction. Meanwhile the response to acetylcholine (ACh) was significantly increased in LBP-treated rats, but the response to nitroprusside had no significant difference among groups. Pretreatment with L-arginine partially restored ACh-induced relaxation in RH rats, but no effect in LBP-treated rats. These results suggested that the role of LBP in decreasing vasoconstriction to PE may be mediated by increase of the effects or/and production of endothelium-derived relaxation factor (EDRF). LBP increased formation of EDRF may be related to increase the substrate of EDRF.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Hypertension, Renovascular/metabolism , Nitric Oxide/metabolism , Polysaccharides/pharmacology , Animals , Aorta/metabolism , Drugs, Chinese Herbal/chemistry , In Vitro Techniques , Male , Phenylephrine , Polysaccharides/isolation & purification , Random Allocation , Rats , Rats, Wistar , Solanaceae/chemistry , Vasoconstriction/drug effectsABSTRACT
The inhibitory activities of more than 40 species of Chinese medicinal herbs or their single chemical components against simian immunodeficiency virus (SIV) have been studied. The study revealed that four species of the medicinal herbs and a single chemical component had more than 50% inhibition of SIV antigen expression and five other herbs' inhibitory rate of SIV antigen expression was between 30-50%. The results showed that Chinese medicinal herbs could inhibit the SIV activity.