Physiology and Pharmacology
Volume:16 Issue: 3, 2013

It is well known that the metabolic factors play an important role in the regulation of angiogenesis. Increased metabolic activity leads to decreased oxygen levels and causes tissue hypoxia. Hypoxia starts different signals to stimulate angiogenesis and promotes oxygen delivery to tissues. It has been suggested that released adenosine from hypoxic tissues plays a vital role in angiogenesis. In this context, the following feedback control hypothesis is proposed: Under hypoxic conditions, membrane 5´-nucleotidase dephosphorylates AMP to adenosine in the extracellular space of a cardiomyocyte, hepatocyte or other parenchymal cells. Extracellular adenosine binds and stimulates adenosine receptor that leads to the release of vascular endothelial growth factor (VEGF) from the parenchymal cell. Binding of VEGF to its receptor on the surface of endothelial cells activates proliferation and migration of these cells. Adenosine can also activate the proliferation of vascular endothelial cells through mediating other anti and proangiogenic growth factors. Adenosine can also induce vasodilation and play a role in the vascular growth and remodeling. After establishment of a new capillary network, adenosine, VEGF and other pro and antiangiogenic growth factors return to near basal concentrations, and then the angiogenesis process terminates. In some conditions up to 50–70% of the hypoxia-induced angiogenesis mediates through adenosine. Hence, the main aim of this review is to focus on the physiological role of adenosine and its receptors in the induction of angiogenesis under hypoxic conditions

Minocycline is a derivative of tetracycline that has anti-inflammatory, antiappoptic, antioxidant and neuroprotective effects. Since there is a relationship between cell death and seizure, the aim of this study was to examine the role of minocycline in development of amygdala kindling in Wistar rats. In this study, 21 rats were divided into three groups. After sterotaxic surgery and 1 week recovery period, rats received kindling stimulations (twice daily at 6 hour intervals). Group 1 (n=7) received daily kindling stimulations. Groups 2 (n=7) and 3(n=7) received saline (1 ml/kg) and minocycline (25 mg/kg), respectively, 60 min before kindling stimulation. Cumulative After discharge Duration (ADD), Cumulative Seizure duration (SD) and Seizure Stage (SS) were recorded and compared to the control group. In group 3, intraperitoneal administration of minocycline for 10 days significantly reduced cumulative ADD (control group: 907.2±64.5, minocycline group: 717.8±67.9) [F(18, 216)=3.5, p<0.001]، and cumulative SD (control group: 999.4±79.8, minocycline group: 776.1±77) [F(19, 228)=3.8, p<0.001] compared to control group (group 2). It also significantly increased the mean number of stimulations to achieve the seizure stage 3 (control group: 7.2±0.6, minocycline group: 11±1) (P<0.05), and 5 (control group: 10.7±0.1, minocycline group: 18.7±0.3) (P<0.001). According to the obtained results, application of minocycline increases the time required for amygdala kindling and may have anticonvulsant effects.

High levels of homocysteine (Hcy) might accelerate dopaminergic cell death through oxidative stress and excitotoxicity. Folate plays an important role in the control of plasma levels of Hcy. In this study, effect of supplementation with folic acid on the 6-hydroxydopamine (6-OHDA)-induced Parkinsonism in rat and also serum level of Hcy was investigated. Rats were fed with folic acid supplements from 1 month before stereotaxic injection of 6-OHDA until to the end of experiments. 6-OHDA was injected into the striatum and development and severity of the Parkinsonism were assessed by conventional behavioral tests. Serum levels of Hcy before surgery and at the end of the behavioral tests were measured. Our results show that 10-fold supplementation, but not 2-fold supplementation of folic acid, significantly attenuates severity of 6-OHDA-induced Parkinsonism. 5-fold supplementation of folic acid also slightly decreased behavioral symptoms of Parkinsonism. Measurement of Hcy levels of sera before surgery show that high intake of folate has no effect on the plasma concentrations of Hcy. However, Hcy in the group of rats that received 10-fold supplement of folic acid was significantly higher than the control group at the end of the behavioral tests. Our results indicate that high intake of folic acid provides anti-Parkinsonism effect in a dose dependent manner, but this effect is not mediated by lowering plasma Hcy.

Recent studies suggest that dietary virgin olive oil (VOO) reduces hypoxia-re oxygenation injury in rat brain. We have attempted to determine the effect of dietary virgin olive oil on brain lipidomics and its relationship with brain edema in a rat stroke model. Five groups, each consisting of 6 male Wistar rats, were studied. The first and second groups (control and sham) received distilled water, while three treatment groups received oral VOO for 30 days (0.25, 0.5 and 0.75 ml/kg/day, respectively). Two hours after the last dose, each main group was subdivided into middle cerebral artery occlusion (MCAO)-operated and intact subgroups for assessment of neuropathology (blood brain barrier permeability) and brain lipid analysis. VOO increased the brain cholesteryl ester and cholesterol levels in doses of 0.5 and 0.75 ml/kg/day. VOO in all three doses increased the brain triglyceride levels (p<0.05). Oral administration of VOO reduces infarct volume, brain edema, blood brain barrier permeability, after transient MCAO in rats. Although further studies are needed to clarify the mechanisms of ischemic tolerance, VOO is partly associated with increased levels of brain cholesteryl ester, cholesterol and triglyceride in rats.

There is currently a debate over the interaction between Ca2+ channels and cannabinoid system on learning and memory processing. In this study, we examined the effect of acute injection of cannabinoid agonist (Win- 55212-2) (Win) or antagonist (AM251), following chronic injection of verapamil, as a L-type Ca2+ channels blocker, on passive avoidance (PA) test in male Wistar rats. Male Wistar rats weighing 200-250 g were used. The animals were randomly divided into two main groups. Firstly, these two groups were treated with i.p injection of verapamil (25 mg/kg) or saline for 13 days (once daily). Before PA training, each group was divided into three subgroups, which received verapamil (or saline), Win (1 mg/kg) or AM251 (1 mg/kg). Then, PA training (acquisition test) was performed and retrieval test was done 24 h after the training. The results showed that Win as a cannabinoid receptor agonist and verapamil as an L-type Ca2+ channels blocker decreased the acquisition and retrieval of PA task, but AM251 as a cannabinoid antagonist improved PA task. Meanwhile, acute use of an antagonist, simultaneous with verapamil, prevent verapamil induced PA impairment effect. The results of the present study indicate that acute injection of cannabinoid agonist and chronic injection of verapamil decrease memory in the PA task, whereas acute injection of cannabinoid antagonist has the opposite effect on memory. Furthermore, there is an interaction between functions of L-type Ca2+ channels and cannabinoid system on learning and memory.

Febrile seizures are the most common seizure disorder in childhood and its prevalence is estimated to be 2 to 5 percent. There is a relationship between the use of corticosteroids and seizures. This study investigated the effects of dexamethasone pretreatment on convulsive behavior caused by hyperthermia. In this study, 24 rats aged 19-20 days were divided into 3 groups (n=8) as control, hyperthermia and dexamethasone. In the hyperthermia group, rats were placed in the chamber for 30 min and warm wind was blown on them. In the dexamethasone group, the rats received intraperitoneal dexamethasone before hyperthermia. The body temperature of the rats was continuously recorded via a rectal probe throughout the experiment. During 30 min of hyperthermia, behavior of each rat was carefully observed and recorded. Blood sampling was done from the heart and samples were used to measure histamine blood levels. All the rats that were exposed to hyperthermia showed convulsive behavior. Dexamethasone potentiated seizure intensity and significantly increased the rate of tonic-clonic seizure (5.62±1.05 in dexamethasone and 1.37±0.46 in hyperthermia) (p=0.02). Hyperthermia decreased histamine blood levels and dexamethasone potentiated this reduction (p<0.001). At least one of the ways that hyperthermia leads to seizure is through the reduction of histamine blood level. Since histamine has an anticonvulsant effect, reduction of histamine blood level is one reason of hyperthermia -induced seizure. Dexamethasone leads to a deacrease in histamine blood level and potentiates hyperthermia-induced seizure.

Orexin A is a hypothalamic neuropeptide, widely distributed in many parts of the central nervous system and perhaps due to this reason, this neuropeptide is involved in many physiological functions. The purpose of this study was to determine the effect of lateral cereberoventricular injection of orexin A on distance, velocity and swimming time in rats. The results were analyzed by one way ANOVA and Tukey HSD tests. P≤ 0.05 was considered as the level of significance. 30 adult male Wistar rats (200 ± 20 g) were randomly divided into three groups of orexin, sham and control. The orexin and sham groups were placed in a stereotaxic apparatus and a cannula was inserted into their right cerebral ventricle. Lateral cerebroventricular injections were performed with 3 nmol orexin A and 3 nmol aCSF in orexin and sham groups, respectively. Afterwards, rats of 3 groups individually swam for 30 minutes and the distance, velocity and swimming time were measured by Etheovision. Lateral cerebroventrivular injection of orexin A caused significant increases in distance and velocity of swimming, however, it had no effect on swimming time. Lateral cerebroventricular injection of orexin A significantly increased distance and velocity of swimming, without any effect on swimming time in rats.

Different ATP-sensitive potassium channels have been detected in the mitochondrial inner membrane of cells. They are suggested to be involved in cell processes including cell protection. Here, we characterized the biophysical and electropharmacological properties of a KATP channel in the brain mitochondrial inner membranes. After removing and homogenizing the rat brain, the supernatant was separately centrifuged in MSE digitonin, H2O and Na2CO3 and mitochondrial inner membrane vesicles were obtained in MSE solution. L-α- Phosphatidylcholine (membrane lipid) was extracted from fresh egg yolk. Bilayer lipid membranes were formed in a 150 μm diameter hole. All recordings were filtered at 1 kHz and stored at a sampling rate of 10 kHz for offline analysis by PClamp10. Single channel recordings revealed a channel with a slope conductance of 143 ± 7pS in voltage dependent 200 mM KCl cis/50 mM KCl trans. The closed dwell time distributions indicated one and at least two exponential components at positive and negative potentials, respectively. The open dwell time events were fitted to two exponential functions. The block by ATP and glibenclamide characterized this channel as the KATP channel. We also showed that 4- AP and TEA inhibited the channel activities. The activity of channel was not influenced by iberiotoxin, a BK channel blocker, and 5-hydroxydecanoic acid, an inhibitor of mitochondrial ATP-sensitive potassium channels. Western blotting with antibodies directed against Kir6.1 and SUR2B subunits recognized a blocking-peptide-sensitive with a molecular mass of ~55-64kDa and ~120kDa, respectively. This channel is likely to be involved in maintaining proper homeostasis in brain mitochondria and cell processes.

Physalis alkekengi (Solanaceae) is a rich source of various antioxidants. There are some reports that show P. alkekengi has been used for treatment of a wide range of diseases including gout and inflammation. Xanthine oxidase plays a crucial role in gout. Many natural compounds such as various flavonoids have been reported to have inhibitory effect on xanthine oxidase. Different parts of P. alkekengi including leave, calyx, green and orange fruits at different stages of plant growth were gathered from around the Tonekabon, Iran. Then, they were dried in the dark and powdered. Inhibitory effect of various plant extracts on xanthine oxidase activity was measured. Soluble sugar and ascorbic acid contents of plant samples, and their correlation with xanthine oxidase inhibitory effect were also determined. All extracts from different parts of P. alkekengi at the concentration of 0.3 mg/ml had inhibitory effect on xanthine oxidase activity with different degrees from 45% (leaves in the vegetative stage) up to 86.86% (leaves in the green fruit stage and calyxs). The leaves, fruits and calyx stage of maturity contained the highest amount of soluble sugar. Also, maximum amount of total ascorbic acid was displayed in an orange calyx, 12.65 mg.fw-1. These results suggest that extracts of P. alkekengi at different phonological stages have high inhibitory effects on xanthine oxidase activity and they are valuable sources of antioxidant compounds. The green fruit, green calyx and orange calyx had the highest inhibitory effects on the xanthine oxidase activity. Therefore, they are recommended as the most appropriate tissues for the next pharmacological studies.

Several studies have reported anti-anxiety effects of morphine in adult rats. The present study examined the effect of chronic morphine injections in infancy and before puberty on anxiety-like behavior in immature rats. Neonate rats (n=35) were randomly chosen and divided into two groups. On postnatal days 8-14, one group received saline and the other one received morphine. On postnatal day 21, each group was divided into subgroups. These subgroups received either morphine or saline according to the type of group on postnatal days 22-28. Finally, on postnatal days 22 and 28, rate of anxiety was studied in a plus maze. On day 24 after birth, morphine increased percentage of open arm time in all groups (P<0.001). This percentage on day 28 was highest for morphine groups compared with the control group (P<0.001). The number of open arm entry on day 24 after birth was significantly increased, for both groups treated with morphine (P<0.05). The greatest difference was observed on day 28 for re-treated rats with fixed dose of morphine compared to the control group (P<0.001). Locomotor activity on days 24 and 28 after birth for both groups treated with morphine was more than the other groups (P <0.05). Chronic morphine administration in the neonatal period caused reduced anxiety-like behavior in immature rats. Also, re-exposure to morphine at a fixed dose had an age related anti-anxiety effect that increased in older rats.

The interaction between steroid hormones and neurotransmitters such as GABA has been proved. The regulation of muscimol binding to high-affinity GABAA receptors by estradiol and progesterone has been studied within distinct brain regions using in vitro quantitative autoradiography. There are few studies about the mechanism of the effect of steroid hormones on behaviors such as learning and memory and also distribution of GABAAα1 receptor in prefrontal cortex. Therefore, the aim of this study was to evaluate the effect of ovariectomy and passive avoidance learning on distribution of GABAAα1 receptor in prefrontal cortex of rat. Twenty Sprague-Dawley adult rats were randomly divided into four equal groups: intact without learning; intact with learning; ovariectomy without learning and ovariectomy with learning. The shuttle box was used for induction of passive avoidance learning. Immunohistochemical procedure was used for determination of GABAAα1 receptor distribution. Image Analyzer software was used for determination of color intensity. The data showed that ovariectomy lead to a significant (p<0.05) reduction in GABAAα1 receptor distribution in cg1 (cingulate cortex area1), M1 (primary motor cortex) and M2 (secondary motor cortex). While learning in the presence of ovarian hormones induced a significant decrease (p<0.05) in GABAAα1 receptor distribution in Cg1, M1 and M2 of prefrontal cortex of rats, it significantly increased (p<0.05) receptor distribution in the same regions in the absence of ovarian hormones. According to these results ovariectomy and passive avoidance learning change the distribution of GABAAα1 receptor in Cg1, M1 and M2 regions of prefrontal cortex of rat.