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Amaç: Başta hipotalamus olmak üzere merkezi sinir sisteminde geniş bir dağılım gösteren histamin birçok otonomik işlevin düzenlenmesinde bir nörotransmitter veya nöromodülatör olarak rol almaktadır. Hipotalamusta; yiyecek, su alımı ve vücut ağırlığının düzenlenmesinde görev alan birçok çekirdekte histamin reseptörleri geniş bir dağılıma sahiptir. Çalışmada, merkezi yolla histamin, klorfeniramin, ranitidin ve tiyoperamid tedavilerinin sıçanlarda oluşturduğu yiyecek ve su alımı ile vücut ağırlığı değişimleri araştırılmıştır. Gereç ve Yöntemler: Çalışma, Sprague-Dawley ırkı sıçanlarda gerçekleştirilmiştir. Histamin (100 nmol), histaminerjik H1 reseptör antagonisti klorfeniramin (100 nmol), histaminerjik H2 reseptör antagonisti ranitidin (100 nmol) veya histaminerjik H3/H4 reseptör antagonisti tiyoperamid (100 nmol) serebral yan ventriküler yolla günde bir kez olacak şekilde 7 gün boyunca enjekte edilmiştir. Bulgular: Histamin, klorfeniramin ve ranitidinin gıda ve su alımı ile vücut ağırlığında azalmalara neden olmuştur. Fakat tiyoperamid ile yapılan tedavi bahsedilen ilaçların tersine gıda ve su alımı ile vücut ağırlığında artışlara yol açmıştır.Sonuç: Elde edilen veriler, 7 günlük tedaviler sonrasında merkezi histamin, klorfeniramin ve ranitidin tedavilerinin beslenmenin düzenlenmesinde negatif etkilere yol açtığını göstermektedir. Bunun yanında, merkezi tiyoperamid ile yapılan 7 günlük tedavinin gıda ve su alımı ile kilo alımına neden olduğu ortaya çıkmıştır., Aim: The histaminergic system, which has a wide distribution in the central nervous system, especially the hypothalamus, plays a role as a neurotransmitter or neuromodulator in the regulation of many autonomic functions. In the hypothalamus, histamine receptors are widely distributed in many nuclei involved in the regulation of food, water intake, and body weight. In this study, food and water intake and body weight changes caused by histamine, chlorpheniramine, ranitidine, and thioperamide treatments chronically in rats were investigated.Materials and Methods: The study was carried out in Sprague-Dawley rats. Histamine (100 nmol), histaminergic H1 receptor antagonist chlorpheniramine (100 nmol), histaminergic H2 receptor antagonist ranitidine (100 nmol), or histaminergic H3/H4 receptor antagonist thioperamide (100 nmol) were injected via the cerebral side ventricular route for 7 days. Results: Histamine, chlorpheniramine, and ranitidine caused reductions in food and water intake and body weight. However, treatment with thioperamide led to increases in food and water intake and body weight, unlike the aforementioned drugs.Conclusion: As a result, the data obtained show that after 7 days of treatments, central histamine, chlorpheniramine, and ranitidine treatments cause negative effects on the regulation of nutrition. In addition, it was revealed that 7 days of treatment with central thioperamide caused weight gain with food and water intake.

Centrally injected some prostaglandins (PG) and orexin (OX) produce similar cardiovascular responses. We have recently reported that both central cyclooxygenase (COX) and central lipoxygenase (LOX) enzymes mediate the cardiovascular effects of OX. In the current study, we aimed to investigate the mediating effects of thromboxane (TX) A2, PGD, PGE, and PGF2a, as COX pathway subproducts known to be active in cardiovascular control, on cardiovascular responses elicited by OX. Intracerebroventricular (i.c.v.) injection of OX increased cardiovascular levels in normotensive male Sprague Dawley rats. Moreover, central pretreatment with the TXA2 synthesis inhibitor furegrelate, PGF2α receptor antagonist, PGF2α-dimethylamine, PGE, and PGD receptor antagonist AH6809 partially attenuated the centrally administered OX -induced pressor and tachycardic cardiovascular responses in rats. In conclusion, our results show that i.c.v. injection of OX increases blood pressure and heart rate. Moreover, TXA2, PGF2α, PGE, and PGD mediate, at least in part, the centrally applied OX -evoked pressor and tachycardic responses. The results suggest that centrally injected OX -evoked pressor and tachycardia responses may also be mediated by arachidonic acid metabolites other than TXA2, PGF2α, PGE, and PGD.

Merkezi sinir sistemi içerisinde nörotransmitter ve nöromodülatör etkiye sahip histamin, davranış durumunun, biyolojik ritmin, vücut ağırlığının, enerji metabolizmasının, termoregülasyonun, sıvı dengesinin, stresin ve üremenin düzenlenmesinde anahtar role sahiptir. Histaminin merkezi akut enjeksiyonlarının hipotalamo-hipofizer-gonadal (HPG) aks içerisinde etkili olduğunu ve histaminin merkezi H1 ve H2 reseptörlerinin bu etkiye aracılık ettiğini gösterdik. Fakat çalışmalarda, histaminin ve histamin reseptör antagonistlerinin uzun süreli merkezi tedavilerinin HPG aks içerisindeki etkilerine dair açıklayıcı bir bilgi bulunmamaktadır. Çalışmada, kronik olarak intraserebroventriküler (i.s.v.) enjekte edilen histamin ve antagonistlerinin hipotalamo-hipofizer-gonadal (HPG) aksta rol oynayan, gonadotropin salgılatıcı hormonun (GnRH), folikül stimüle edici hormonun (FSH), lüteinleştirici hormonun (LH) ve testosteron hormonunun plazma seviyelerine etkileri araştırılmıştır. Çalışma Sprague-Dawley ırkı sıçanlarda gerçekleştirilmiştir. Histamin (100 nmol), histaminerjik H1 reseptör antagonisti klorfeniramin (100 nmol), histaminerjik H2 reseptör antagonisti ranitidin (100 nmol) veya histaminerjik H3/H4 reseptör antagonisti tiyoperamid (100 nmol) i.s.v. olarak 7 gün boyunca enjekte edilmiştir. Histamin ve antagonistlerinin kronik enjeksiyonu GnRH’nın plazma seviyelerinde anlamlı bir fark oluşturmamıştır. Kronik histamin veya klorfeniramin tedavisi sonucu plazma FSH seviyelerinde artış (p

Brain histamine holds a key position in the regulation of behavioral states, biological rhythms, body weight, energy metabolism, thermoregulation, fluid balance, stress and reproduction in female animals. However, it is not clear whether central histamine exerts any effect on hypothalamic-pituitary-testicular in male rats and if so, the involvement of type of central histamine receptors. The current study was designed to determine the effect of centrally administrated histamine on plasma gonadotropin hormone-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone level, and sperm parameters, and to show the mediation of the central histaminergic H1, H2 and H3/H4 receptors on histamine-evoked hormonal and sperm parameters’ effects. Studies were performed in male Sprague-Dawley rats. A total of 50 or 100 nmol doses of histamine were injected intracerebroventricularly (icv). 100 nmol dose of histamine significantly caused increases in plasma GnRH, LH, FSH and testosterone levels of animals, but not 50 nmol dose of histamine. Moreover, central pretreatment with chlorpheniramine, histaminergic H1 receptor antagonist (100 nmol), ranitidine and histaminergic H2 receptor antagonist (100 nmol) completely prevented histamine evoked increase in plasma GnRH, LH, FSH and testosterone levels, while thioperamide, histaminergic H3/H4 receptor antagonist (100 nmol) pretreatment failed to reverse sex hormones responses to histamine. Both central histamine treatment alone and central histamine treatment after central histaminergic receptors antagonists’ pretreatments did not alter any sperm parameters in rats. In conclusion, our findings show that centrally administered histamine increases plasma GnRH, LH, FSH and testosterone levels of conscious male rats without change any sperm parameters. Moreover, according to our findings, central histaminergic H1, and H2 receptors mediate these histamine-induced effects.

Although L-DOPA revolutionized in the treatment of Parkinson's disease, most patients developed motor complications after several years of treatment. Adjunctive therapy to L-DOPA with drugs related to dopaminergic signaling may reduce its dose without decreasing the therapeutic efficiency and thus ameliorates its adverse effects. It has been shown that 3,4-diaminopyridine (3,4-DAP), a K channel blocker, increased dopamine release from striatal slices by increasing neuronal firing in striatal dopaminergic terminals. The current study investigates whether 3,4-DAP may enhance L-DOPA-induced dopamine (DA) release from striatal slices by increasing neuronal firing in striatal dopaminergic terminals. The effects of L-DOPA and 3,4-DAP on spontaneous DA and DOPAC release were tested in vitro, on acute rat striatal slices prepared from non-treated and 6-hydroxydopamine-pre-treated rats. DA and DOPAC levels were determined by HPLC methods. When 3,4-diaminopyridine was combined with L-DOPA, the observed effect was considerably greater than the increases induced by L-DOPA or 3,4-DAP alone in normoxic and neurodegenerative conditions produced by FeSO4 and 6-hydroxydopamine. Furthermore, L-DOPA plus 3,4-DAP also ameliorated DOPAC levels in neurodegenerative conditions. These data indicate that 3,4 DAP plus L-DOPA activates striatal dopaminergic terminals by increasing the DA release and, thus, could be considered as a promising finding in treatment of acute and chronic injury in dopaminergic neurons.

We previously reported that intracerebroventricularly (ICV) injected arachidonic acid (AA) could produce pressor and bradycardic responses on the cardiovascular system and hyperventilation effect on the respiratory system by activating cyclooxygenase (COX). We also demonstrated that centrally injected AA-induced cardiovascular and respiratory responses were mediated by COX-metabolites, such as thromboxane A2 (TXA2), prostaglandin (PG) D, PGE, and PGF2α. Brain tissue is also able to express the lipoxygenase (LOX) enzyme and LOX-induced AA-metabolites. The current study was designed to investigate the possible mediation of the central LOX pathway in AA-induced cardiorespiratory effects in anesthetized rats. Central pretreatment with different doses of a non-selective LOX inhibitor, nordihydroguaiaretic acid (NDGA) (500 and 1000 μg; ICV) partially blocked the AA (0.5 μmol; ICV)-evoked pressor and bradycardic cardiovascular responses in male anesthetized Sprague Dawley rats. Pretreatment with different doses of NDGA (500 and 1000 μg; ICV) also reduced AA-induced hyperventilation responses, with an increase in tidal volume, respiratory rate and minute ventilation, in the rats. Moreover, AA-induced increasing pO2 and decreasing pCO2 responses were diminished by central NDGA pretreatment. In summary, our findings show that the central LOX pathway might mediate, at least in part, centrally administered AA-evoked cardiorespiratory and blood gases responses.

Nesfatin-1 is a multifunctional neuropeptide having crucial autonomic roles. It is well known that nesfatin-1 collaborates with other central neuromodulatory systems, such as central corticotropin-releasing hormone, melanocortin, oxytocin, and cholinergic systems to show its autonomic effects. Central arachidonic acid cascade plays an important role to provide the homeostasis by exhibiting similar autonomic effects to nesfatin-1. Based on these similarities, the current study was designed to show the effects of intracerebroventricularly (ICV) injected nesfatin-1 on the hypothalamic arachidonic acid (AA) cascade. Immunochemistry and western blot approaches demonstrated that ICV administration of nesfatin-1 provokes an increase in the hypothalamic cyclooxygenase (COX) -1, -2 and lipoxygenase (LOX) protein expression. Moreover, the microdialysis study demonstrated that centrally injected nesfatin-1 increased the posterior hypothalamic extracellular AA products. In conclusion, these findings report that while nesfatin-1 is generating its autonomic effects, it also might be using central prostaglandins and leukotrienes by activating central COX and LOX pathways.

Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A(2), is abundant in the brain and works as a neurotransmitter and/or neuromodulator in the central nervous system. Recently we reported that centrally injected AA generated pressor and hyperventilation effects by activating thromboxane A(2) (TXA(2)) signaling pathway. The present study was designed to investigate the mediation of other metabolites of AA such as prostaglandin (PG) D, PGE and PGF(2 alpha), alongside TXA(2) in the AA-evoked cardiorespiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA caused pressor, bradycardic and hyperventilation responses by increasing pO(2) and decreasing pCO(2) in adult male anaesthetized Sprague Dawley rats. Pretreatment (i.c.v) with different doses of DP/EP prostanoid receptor antagonist, AH6809 or FP prostanoid receptor antagonist, PGF(2 alpha), dimethylamine partially blocked the cardiorespiratory and blood gas changes induced by AA. In conclusion, these data plainly report that central PGD, PGE or PGF(2 alpha) might mediate, at least partly, centrally administered AA-evoked cardiorespiratory and blood gas responses.

Phoenixin (PNX) and nesfatin-1 are localised in the hypothalamus and the pituitary gland. Moreover, the most of the PNX-expressing neurons in the hypothalamus also co-express nesfatin-1. These outcomes may suggest that there is an interaction between PNX and nesfatin-1, at least in terms of neuroendocrine-mediated regulations. Hence, the study was planned to find out the effects of centrally delivered PNX and nesfatin-1 on male sex hormones or to show the interactive association of intracerebroventricularly (ICV) injected PNX+nesfatin-1 combination on the release of male hormones. PNX and nesfatin-1, single or together, were delivered ICV to different male Wistar Albino rat groups. Both PNX and nesfatin-1 induced a significant enhancement in plasma FSH, LH and testosterone without inducing any alteration in plasma GnRH in the rats. The central combinatorial treatment of both the neuropeptides produced a more potent rise in male plasma hormone levels than treating with single neuropeptide. In summary, our preliminary data show that centrally delivered PNX and nesfatin-1 can affect plasma male hormone levels. Moreover, that the combinatorial treatment with both the neuropeptides in male rats leading to a more potent effect on the plasma male hormone levels might suggest that both these neuropeptides act synergistically in terms of regulation of male HPGA.

The current study was designed to determine the effect of centrally chronic-administrated histamine and histaminergic receptors antagonist on the hypothalamic cyclooxygenase (COX) and lipoxygenase (LOX) enzymes amount. Studies were performed in male Sprague–Dawley rats. Histamine (100 nmol), histaminergic H1 receptor antagonist chlorpheniramine (100 nmol), histaminergic H2 receptor antagonist ranitidine (100 nmol) or histaminergic H3/H4 receptor antagonist thioperamide (100 nmol) was injected intracerebroventricularly for 7 days. Central chronic histamine treatment caused an increase in all three enzymes amount in the hypothalamus. Histaminergic receptors antagonist chronic-treatments with chlorpheniramine, ranitidine and thioperamide produced to decrease in hypothalamic COX-1 amount and to increase in hypothalamic COX-2 and LOX amounts. In conclusion, our findings show that the central histaminergic system has a potential for effect the central COX and LOX pathways. This could be interpreted that central histaminergic and central COX and LOX pathways have an interaction to regulate in many central nervous system functions.

Saccharomyces cerevisiae ve fitaz ayri ayri olarak broiler tavuklarda yem katkisi amaciyla kullanilmakta-dir. Bu arastirma, farkli oranlarda S. cerevisiae’nin ve fitaz kombinasyonunun broiler tavuklarda buyume per-formansi, plazma biyokimyasal parametreleri ve plazma enzim aktiviteleri uzerindeki etkisini degerlendirmek icin yapildi. Calisma boyunca hayvanlar ad libitum beslendi. 1 gunluk yasta 600 adet broiler tavuk rastgele se-cildi ve 8 gruba sirasiyla su sekilde ayrildi: Kontrol (C); Fitaz (P) (200 g Fitaz 1000 kg yeme ilave edildi); S. cerevisiae (Y1) (% 0,1 oraninda S. cerevisiae yeme ilave edildi); Y1+P (grup Y1 ve P’nin kombinasyonu); Y2 (% 0,2 oraninda S. cerevisiae yeme ilave edildi); Y2+P (grup Y2 ve P’nin kombinasyonu); Y4 (% 0,4 oraninda S. cerevisiae yeme ilave edildi); Y4+P (grup Y4 ve P’nin kombinasyonu). Calismanin sonlandirildigi 42. gunde, her gruptan rastgele secilen 15 adet hayvanin brahial veninden kan ornekleri alindi. Kan orneklerinin plazmasi ayrildi ve biyokimyasal parametreler ve enzim aktivitelerinin olculmesi icin kullanildi. S. cerevisiae, tek basina ve S.cerevisiae ve fitaz kombinasyonlari, Y4 grubu haric, ozellikle 6. haftada tavuklarda canli agirlik ve canli agirlik kazanimini arttirdi. Sadece fitaz ve/veya S. cerevisiae ve kombinasyonlarinin verildigi tavuklarda plazma trigliserid, total kolesterol, LDL_kolesterol, glukoz, kalsiyum ve GGT enzimi azalirken, hayvanlarda yuksek duzeyde HDL-kolesterol, fosfor ve ALT enzimi tespit edildi. Diger taraftan, tavuklarda sadece fitaz ve/veya S. cerevisiae ve kombinasyonlarinin yem katkisi olarak kullanilmasi, hematokrit, plazma protein ve AST enzim degerlerini degistirmedi. Sonuclar fitaz ve S. cerevisiae’nin yalniz ve/veya kombinasyonlarinin yem katkisi olarak kullanilmasinin buyume performansi ve canli agirlik kazanimini arttirdigini goster-mektedir. Boylece, S.cerevisiae ve fitaz kombinasyonlari buyumeyi arttirici olarak kullanilabilir. Ancak, maya ve fitaz kombinasyonlarinin buyumedeki etkisinin ortaya konmasi icin daha fazla calismanin yapilmasi gerekmektedir.

Nesfatin-1, a peptide whose receptor is yet to be identified, has been shown to be involved in the modulation of feeding, stress, and metabolic responses. Recently, increasing evidence has supported a modulatory role of nesfatin-1 in cardiovascular activity. We have previously reported that nesfatin-1 causes an increase in blood pressure in normotensive and hypotensive rats by increasing plasma catecholamine, vasopressin, and renin levels. Recent reports suggest that nesfatin-1 may activate the central cholinergic system. However, there is no evidence showing an interaction between central nesfatin-1 and the cholinergic system. Therefore, this study aimed to determine whether the central cholinergic system may have a functional role in the nesfatin-1-induced cardiovascular effect observed in normotensive rats. Intracerebroventricular injection of nesfatin-1 caused short-term increases in mean arterial pressure and heart rate responses including bradycardic/tachycardic phases in normotensive animals. Central injection of nesfatin-1 increased the acetylcholine and choline levels in the posterior hypothalamus, as shown in microdialysis studies. Central pretreatment with the cholinergic muscarinic receptor antagonist atropine and/or nicotinic receptor antagonist mecamylamine blocked nesfatin-1-induced cardiovascular effects. In conclusion, the results show that centrally administered nesfatin-1 produces a pressor effect on blood pressure and heart rate responses including bradycardic/tachycardic phases in normotensive rats. Moreover, according to our findings, the central cholinergic system can modulate nesfatin-1-evoked cardiovascular activity.

Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin–angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus—a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system—in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague–Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect. Therefore the current study was designed to investigate the possible effects of centrally injected CDP-choline on respiratory system and the mediation of the central cholinergic receptors and phospholipase to thromboxane signaling pathway on CDP-choline-induced respiratory effects in anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP-choline induced dose- and time-dependent increased respiratory rates, tidal volume and minute ventilation of male anaesthetized Spraque Dawley rats. I.c.v. pretreatment with atropine failed to alter the hyperventilation responses to CDP-choline whereas mecamylamine, cholinergic nicotinic receptor antagonist, mepacrine, phospholipase A 2 inhibitor, and neomycin phospholipase C inhibitor, blocked completely the hyperventilation induced by CDP-choline. In addition, central pretreatment with furegrelate, thromboxane A 2 synthesis inhibitor, also partially blocked CDP-choline-evoked hyperventilation effects. These data show that centrally administered CDP-choline induces hyperventilation which is mediated by activation of central nicotinic receptors and phospholipase to thromboxane signaling pathway.

Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A

CDP-choline is an endogen molecule and also a drug that is used in several trauma and ischemic conditions. It has been demonstrated that it improves the hemodynamic parameters in different shock models and prevents tissue damage in rats. The current study tested the effect of CDP-choline on hypotension, inflammation and tissue injury induced by septic shock model in rats. Twenty-four adult, male Spraque-Dawley rats, weighing 250-300 g were used. Septic shock was induced by cecal ligation-incision (CLI). CDP-choline (100 mg/kg) injected intravenously (i.v.) at the 180th minute of the experiment. The animals were observed for 180 minutes after the injection, then blood and tissue samples were obtained for cytokine measurements and histological examinations, respectively. The cecal ligation-incision decreased arterial pressure and increased heart rate. Intravenous injection of CDP-choline reversed hypotension and increased arterial pressure up to control levels within the first 60 minutes without changing the increase in heart rate. The effect lasted for 3 hours. CDP-choline attenuated the increases in TNF-α, IL-1β and IL-6 levels in septic shock. Moreover, the drug exerted protective effects for the injury induced by septic shock in lungs, liver and kidney tissues; whereas this effect was not present on spleen. In conclusion, the present data suggested that intravenous CDP-choline administration can improve the deteriorations in hemodynamic and inflammatory parameters and can prevent the tissue injury in septic shock-induced by CLI in rats, CDP-kolin, endojen bir molekül olmasının yanısıra travma ve iskemik koşullarda da kullanılan bir ilaçtır. Değişik şok modellerinde, sıçanlarda hemodinamik parametreleri iyileştirdiği ve doku hasarına karşı koruyucu etki gösterdiği ortaya konmuştur. Bu çalışmada, CDP-kolin’in sıçanlarda septik şokun neden olduğu hipotansiyon, inflamasyon ve doku hasarı üzerine olan etkileri incelendi. Deneylerde, ağırlıkları 250-300 g arasında değiş en 24 adet Spraque-Dawley ırkı erkek sıçan kullanıldı. Septik şok modeli oluşturmak için çekal bağlama-kesme yöntemi uygulandı. CDP-kolin (100 mg/kg), deneyin 180. dakikasında intravenöz (i.v.) olarak uygulandı. Hayvanlar enjeksiyon sonrası 180 dakika daha gözlendikten sonra sitokin ölçümleri ve histolojik incelemeler için sırasıyla kan ve doku örnekleri toplandı. Çekal bağlama-kesme kan basıncını azaltırken kalp atım sayısını artırdı. İntravenöz CDP-kolin uygulaması hipotansiyonu düzeltti ve arteryel basıncı ilk 60 dakika içerisinde, kalp hızındaki yüksekliği değiştirmeden, kontrol düzeylerine kadar artırdı. Etki 3 saat kadar sürdü. CDP-kolin, septik şoktaki TNF-α, IL-1β ve IL-6 düzeylerindeki yükselmeleri de azalttı. Bu etkilere ek olarak ilaç; akciğer, karaciğer ve böbreklerde (ancak dalakta değil) septik şokun sebep olduğu hasara karşı koruyucu etki gösterdi. Sonuç olarak mevcut veriler intravenöz CDP-kolin uygulamasının; çekal bağlama-kesme ile oluşturulan septik şokun neden olduğu hemodinamik ve inflamatuar parametrelerdeki bozukluklarda iyileşmeye ve meydana gelen doku hasarına karşı koruyucu olduğunu ortaya koymaktadır

The purpose of the current study is to investigate the functional connections between the central histaminergic and cholinergic systems at NTS level in hypotensive condition. Experiments were carried out in male Wistar Albino rats. The hypotension was achieved by withdrawing a total volume of 1.5 ml blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in NTS area to measure extracellular ACh and Ch levels. The hemorrhage produced a severe and long-lasting decrease in mean arterial blood pressure (MAP) and increase in extracellular ACh and Ch levels in NTS. Administration of histamine intracerebroventricularly (i.c.v.) or into the NTS reversed the hemorrhagic hypotension by increasing MAP and heart rate. I.c.v. injection of histamine also caused the additional increase in extracellular ACh and Ch levels. Moreover, central histamine injection augmented intracytoplasmic AChE immunoreactivity in NTS. These changes were completely blocked by histaminergic H1 receptor antagonist chlorpheniramine, but histaminergic H2 receptor blocker ranitidine and histaminergic H3/H4 receptor antagonist thioperamide failed to produce these effects. In conclusion, these findings are interpreted that brain histaminergic H1 receptor activation by central histamine injection may promote cholinergic stimulation in the NTS and subsequently reverses the hypotension.

Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Sprague Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA(2) signaling pathway. (C) 2016 Elsevier B.V. All rights reserved.

This study investigated the cardiovascular effects of nesfatin-1 in normotensive rats and animals subjected to hypotensive hemorrhage. Hemorrhagic hypotension was induced by withdrawal 2 mL blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP) and heart rate (HR). Intracerebroventricularly (i.c.v.) administered nesfatin-1 (100 pmol) increased MAP in both normotensive and hemorrhaged rats. Nesfatin-1 also caused bradycardia in normotensive and tachycardia in hemorrhaged rats. Centrally injected nesfatin-1 (100 pmol, i.c.v.) also increased plasma catecholamine, vasopressin and renin concentrations in control animals and potentiated the rise in all three cardiovascular mediators produced by hemorrhage. These findings indicate that centrally administered nesfatin-1 causes a pressor response in conscious normotensive and hemorrhaged rats and suggest that enhanced sympathetic activity and elevated vasopressin and renin concentrations mediate the cardiovascular effects of the peptide.

The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3–H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A 2 . Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A 2 (TXA 2 ) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H 2 receptor antagonist ranitidine (50nmol; i.c.v.) almost completely and H 3 /H 4 receptor antagonist thioperamide (50nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H 1 receptor blocker chlorpheniramine (50nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.