Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with baroreflex dysfunction and multiple cardiac diseases such as diabetic myocardiopathy. In the present study, we aimed to explore the role of peripheral NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in peripheral cardiovascular control, in baroreflex sensitivity (BRS) of streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for 4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function, BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to increased plasma NPY and lipid level. And the STZ-increased lipid levels were reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but had little effect on the impaired cardiac function of the STZ rats. BIIE 0246 alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced aberrant baroreflex control of heart rate in the STZ rats. In addition, BIIE 0246 alleviated the bradycardia, but further impaired cardiac contractility in the STZ rats. These results suggest that peripheral Y1R and Y2R play different roles in STZ-induced impairment of BRS.

It has been reported that the frequency modulation (FM) or FM direction sensitivity and forward masking of central auditory neurons are related with the neural inhibition, but there are some arguments, because no direct evidence of inhibitory synaptic input was obtained in previous studies using extracellular recording. In the present study, we studied the relation between FM direction sensitivity and forward masking of the inferior collicular (IC) neurons using in vivo intracellular recordings in 20 Mus musculus Km mice. Thirty seven with complete data among 93 neurons were analyzed and discussed. There was an inhibitory area which consisted of inhibitory postsynaptic potentials (IPSP) at high frequency side of frequency tuning of up-sweep FM (FMU) sensitive neurons (n = 12) and at low frequency side of frequency tuning of down-sweep FM (FMD) selective neurons (n = 8), while there was no any inhibitory area at both sides of frequency tuning of non-FM sweep direction (FMN) sensitive neurons (n = 17). Therefore, these results show that the inhibitory area at low or high frequency side of frequency tuning is one of the mechanisms for forming FM sweep direction sensitivity of IC neurons. By comparison of forward masking produced by FMU and FMD sound stimuli in FMU, FMD and FMN neurons, the selective FM sounds could produce stronger forward masking than the non-selective in FMU and FMD neurons, while there was no forward masking difference between FMU and FMD stimuli in the FMN neurons. We suggest that the post-action potential IPSP is a potential mechanism for producing stronger forward masking in FMU and FMD neurons.

P2X7 receptor is a member of ATP-gated non-selective cation channels. P2X7 receptor is widely distributed in vivo, and its expression is always observed to be up-regulated in the pathological inflammatory circumstances. P2X7 receptor has an unusual property of forming membrane pore during prolonged agonist exposure or high concentrations of agonist activation, different from other members of P2X receptors (P2X1-6). Because of this property, P2X7 receptor has been implicated in inflammatory cytokine release, and is closely related to inflammatory diseases. With the wide application of the P2X7-knockout animal model and specific P2X7 receptor antagonists in inflammatory disease research, P2X7 receptor is emerging as a new target for the treatment of inflammatory diseases. This article will review the recent progress regarding the effect of P2X7 receptor on inflammatory diseases and its mechanism.

Depression is a very common mental health problem in our modern society. Stress is involved in the provocation of depression. The pathogenesis of depressive disorder is still not well known. The development of neuroendocrine immunology opens a new sight for clarification of mechanism underlying stress-induced depression. Chronic stress activates peripheral and central immune systems accompanied with the release of inflammatory mediators, including cytokines. Activated immune system mediates the process of depression through the interaction with neuron system and neuroendocrine system, including regulating the monoamine neurotransmitter system in synthesis, metabolism and reuptake, inducing the overactivation of hypothalamus-pituitary-adrenal (HPA) axis and its negative feedback regulation, and reducing neurogenesis. This present paper reviews the cytokines mechanisms underlying stress-induced depression.

Vascular adventitial fibroblasts (AF) differentiation to myofibroblasts (MF) is the critical physiopathologic feature of vascular remodeling. This study was to investigate the role of RhoA-Rho kinase signaling pathway in AF differentiation to MF induced by transforming growth factor β1 (TGF-β1). The results showed that TGF-β1 up-regulated total RhoA protein expression and RhoA activity in cultured AF by Western blotting and Rho pull-down assay, respectively. TGF-β1 up-regulated phospho-Myosin phosphatase target subunit (MYPT1, a downstream substrate of Rho kinase) expression without altering Rho kinase protein expression, indicating TGF-β1 induced the enhancement of activity of Rho kinase. Ad-N19RhoA-hrGFP virus infection and Y27632, a specific inhibitor of Rho kinase, dose-dependently inhibited TGF-β1-induced α-SM-actin and Calponin expression, as markers of MF differentiation. In conclusion, the RhoA-Rho kinase pathway is involved in AF differentiation to MF induced by TGF-β1.

Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).

The cardiac inwardly rectifying potassium channel (I(K1)), which is mainly expressed in mammalian atrial and ventricular myocytes, has been considered as the primary conductance controlling the resting potential (RP) and permitting a significant repolarizing current during the terminal phase of action potential. Therefore, I(K1) is highly influential on the RP, and the modulation of I(K1) would likely have profound effects on cardiac excitability and arrhythmogenesis. This article may shed light on the fundamental properties of cardiac I(K1), the mechanisms of inward rectification and I(K1) subunits composition. Furthermore, the article discusses the role of I(K1) in ventricular excitability and arrhythmogenesis and explores the possibility of modulating I(K1) as an antiarrhythmic mechanism. In fact, both blocking and enhancing I(K1) could be antiarrhythmic, but have proarrhythmic potential at the same time. Action potential duration (APD) prolongation has been accepted as an important antiarrhythmic strategy with some evidence in animal models of arrhythmogenesis that I(K1) blockade can prolongate APD and be antiarrhythmic. However, the potential of I(K1) blockade has not resulted in the development of specific I(K1) blockers used clinically. Safety concerns are probably the main reason, and the therapeutic potential for I(K1) blockers seems somewhat small. On the contrary, the up to date reports indicate that moderately activating I(K1) and hyperpolarizing the RP which has been depolarized by pathologic injury are to be feasible and effective to alleviate some kinds of ventricular arrhythmias.

The aim of the present study was to explore the changes and roles of dystrophin and membrane permeability in hypoxic training. Seventy-two 8-week-old Sprague Dawley (SD) rats were randomly divided into 4 groups, normoxic non-train (NC), normoxic train (NT), hypoxic non-train (HC), and hypoxic train (HT) groups. The rats of each group were randomly divided into three subgroups, non-exhaustive, low-speed exhaustive test and high-speed exhaustive test subgroups. Rats in hypoxia groups lived and were trained in a condition of 12.7% oxygen concentration (equal to the 4 300 m altitude). NT and HT groups received 4 weeks of training exercise. Then the rats in all non-exhaustive subgroups were sacrificed, and gastrocnemii were sampled for the measurements of lactate dehydrogenase (LDH), succinatedehydrogenase (SDH), malate dehydrogenase (MDH) activities. Moreover, serum LDH activity was analyzed. Low-speed exhaustive test and high-speed exhaustive test subgroups received exhaustive tests with 20 (71% VO2max) and 30 m/min speed (86% VO2max), respectively, and their exhaustive times were recorded. The results showed that, compared with normoxic groups, the weights in hypoxia groups exhibited slower increase. The level of dystrophin in HT group without exhaustion test didn't change significantly. The muscle MDH activities were markedly affected by the different oxygen concentration, training and their interaction (P < 0.05), whereas the muscle LDH activities were only affected by the different oxygen concentration (P < 0.05). Serum LDH activities were affected by the interaction of the different oxygen concentration and training (P < 0.05), showing decreased muscle LDH and increased blood LDH activities. The exhaustion time were markedly affected by the different test speed, training and their interaction (P < 0.05), and also affected by the interaction of the different oxygen concentration and training (P < 0.05), but didn't affected by oxygen concentration. The exhaustive time of HT high-speed exhaustive test subgroup was more than NT high-speed exhaustive test subgroup in 30 m/min exhaustion test. Compared with NT high-speed exhaustive test subgroup, HT high-speed exhaustive test subgroup had an earlier fatigue in the test, but had a rapid recovery. These results suggested that hypoxic training can effectively increase the rats' high-speed exhaustive time. The mechanism may be related to an increase in serum LDH caused by the increased membrane permeability after hypoxic training.

To investigate the mechanisms underlying the cholinergic agonist carbachol-induced cardiovascular responses, changes of renin-angiotensin system were examined in fetal hormonal systems. In the ovine fetal model under stressless condition, the cardiovascular function was recorded. Blood samples were collected before (during baseline period) and after the intravenous administration of carbachol. Simultaneously, the levels of angiotensin I (Ang I), angiotensin II (Ang II) and vasopressin in the fetal plasma were detected by immunoradiological method. Also, blood gas, plasma osmolality and electrolyte concentrations were analyzed in blood samples. Results showed that in chronically prepared ovine fetus, intravenous infusion of carbachol led to a significant decrease of heart rate (P < 0.05), and a transient decrease followed by an increase of blood pressure (P < 0.05) within 30 min. After the intravenous infusion of carbachol, blood concentrations of Ang I and Ang II in near-term ovine fetus were both significantly increased (P < 0.05); however, blood concentration of vasopressin, values of blood gas, electrolytes and plasma osmolality in near-term ovine fetus were not significantly changed (P > 0.05). Blood levels of Ang I and Ang II in the atropine (M receptor antagonist) + carbachol intravenous administration group was lower than those in the carbachol group without atropine administration (P < 0.05). In conclusion, this study indicates that the near-term changes of cardiovascular system induced by intravenous administration of carbachol in ovine fetus, such as blood pressure and heart rate, are associated with the changes of hormones of circulatory renin-angiotensin system.

Ischemia-reperfusion injury (IRI) has been recognized as a serious problem for therapy of cardiovascular diseases. Calcium regulation appears to be an important issue in the study of IRI. This article reviews calcium regulation in myocardial and vascular IRI, including the calcium overload and calcium sensitivity in IRI. This review is focused on the key players in Ca(2+) handling in IRI, including membrane damage resulting in increase in Ca(2+) influx, reverse-mode of Na(+)-Ca(2+) exchangers leading to increased Ca(2+) entry, the decreased activity of sarcoplasmic reticulum (SR) Ca(2+)-ATPase causing SR Ca(2+) uptake dysfunction, and increased activity of Rho kinase. These key players in Ca(2+) homeostasis will provide promising strategies and potential targets for therapy of cardiovascular IRI.