CDP-kolin'in merkezi kardiyovasküler ve solunum düzenlenmesindeki rolü: Etkide merkezi prostaglandinerjik sistemin aracılığı
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Date
2013
Authors
Topuz, Bora Burak
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Publisher
Uludağ Üniversitesi
Abstract
Sitidin-5‟-difosfatkolin (CDP-kolin), membran fosfatidilkolinin ara ürünü olan ve endojen olarak sentezlenen bir mononükleotiddir. Son yıllarda merkezi veya periferik yollarla uygulanan CDP-kolin‟in kardiyovasküler sistem üzerinde pressör bir etki oluĢturduğu ve bu etkilerine kolinerjik sistemin aracılık ettiği gösterilmiĢtir. Merkezi prostaglandinerjik sistemde normatansif sıçanlarda merkezi prostaglandinerjik reseptörleri ve kısmende merkezi kolinerjik nikotonik reseptörleri aktive ederek pressör ve bradikardik bir yanıta neden olmaktadır. Bu çalıĢmada ise normatansif sıçanlarda merkezi olarak enjekte edilen ve bir kolin donörü olan CDP-kolin‟in kardiyovasküler ve solunum sistemi üzerine etkilerini ve CDP-kolin tarafından indüklenen bu etkilerde merkezi prostaglandinerjik sistemin aracılığını belirlemek amaçlanmıĢtır. ÇalıĢmada erkek Spraque-Dawley cinsi sıçanlar kullandı. Serebral yan ventriküle (s.y.v.) enjekte edilen CDP-kolin (0.5, 1 and 2 µmol) zamana ve doza bağlı olarak kardiyovasküler sistem üzerinde pressör ve bradikardik etkiye neden olurken, normatansif sıçanların solunum sayısı, tidal volümü ve dakika solunum volümünde artıĢa neden oldu. Yine merkezi olarak enjekte edilen CDP-kolin posterior hipotalamustan yapılan mikrodiyaliz çalıĢmasına göre posterior hipotalamik ekstrasellüler total prostaglandin konsantrasyonunda % 62‟lik bir artıĢ oluĢturdu. Ayrıca fosfolipaz A2 (FLA2) inhibitörü, mepakrin (250 µg; s.y.v.), fosfolipaz C (FLC) inhibitörü, neomisin (250 µg; s.y.v.) ve seçici olmayan siklooksijenaz (COX) inhibitörü, ibuprofen (200 µg; s.y.v.) ile yapılan ön tedavi CDP-kolin‟in oluĢturduğu kardiyovasküler ve solunum etkilerini tamamen engellerken, tromboksan A2 (TXA2) sentez inhibitörü, furegrelate (250 µg; s.y.v.) ile yapılan ön tedavi ise CDP-kolin‟in oluĢturduğu kardiyovasküler ve solunum etkilerini azalttı. Sonuç olarak, elde edilen bulgular merkezi olarak uygulanan CDP-kolin‟in kardiyovasküler sistem üzerine bradikardik ve pressör bir yanıt, solunum sistemi üzerine ise solunum sayısı, tidal volüm ve dakika solunum volümünde arttırıcı bir etki oluĢturduğunu göstermektedir. Ayrıca elde edilen bulgulara göre CDP-kolin tarafından indüklenen kardiyovasküler ve solunum sistemi üzerine olan etkilerde, merkezi prostaglandinerjik sistemin aracılığı vardır.
Cytidne-5‟-diphosphocholine (CDP-choline) is an endogenously synthesized mononucleotide and intermediate product of membrane phosphatidylcholine. Recently it was demonstrated that centrally or peripherally administrated CDP-choline caused pressor effect and cholinergic system mediated these effects of it. Also central prostaglandinergic system leads to pressor and bradycardic response by activating totally central prostaglandinergic receptors and partly central cholinergic nicotinic receptors in normotensive rats. The main object of the present study was to determine the effect of centrally injected CDP-choline on cardiorespiratory system and the mediation of the central prostaglandinergic system on CDP-choline, as a choline donor, -induced cardiorespiratory effects in normotensive rats. Experiments were carried out in male Spraque Dawley rats. Intracerebroventricularly (i.c.v.) injected CDP-choline (0.5, 1 and 2 µmol) caused dose- and time-dependent pressor and bradycardic effect on cardiovascular system and increased respiratory rates, tidal volume and minute ventilation of normotensive rats. Also centrally injected CDP-choline accompanied by 62 % increase in extracellular total prostaglandin concentration in the posterior hypothalamus, as shown in microdialysis studies. Moreover, phospholipase A2 inhibitor mepacrine (250 µg; i.c.v.), phospholipase C inhibitor neomycine (250 µg; i.c.v.) and nonselective COX inhibitor ibuprofen (200 µg; i.c.v.) almost completely and thromboxane A2 synthesis inhibitor furegrelate (250 µg; i.c.v.) decreased CDP-cholineevoked cardiorespiratory effects. In conclusion, results show that centrally administered CDP-choline evokes pressor and bradycardic response on cardiovascular system and increases respiratory rates, tidal volume and minute ventilation in normotensive rats. Moreover, according to our findings, there is an involvement of the central prostaglandinergic system in CDP-choline-induced cardiorespiratory responses.
Cytidne-5‟-diphosphocholine (CDP-choline) is an endogenously synthesized mononucleotide and intermediate product of membrane phosphatidylcholine. Recently it was demonstrated that centrally or peripherally administrated CDP-choline caused pressor effect and cholinergic system mediated these effects of it. Also central prostaglandinergic system leads to pressor and bradycardic response by activating totally central prostaglandinergic receptors and partly central cholinergic nicotinic receptors in normotensive rats. The main object of the present study was to determine the effect of centrally injected CDP-choline on cardiorespiratory system and the mediation of the central prostaglandinergic system on CDP-choline, as a choline donor, -induced cardiorespiratory effects in normotensive rats. Experiments were carried out in male Spraque Dawley rats. Intracerebroventricularly (i.c.v.) injected CDP-choline (0.5, 1 and 2 µmol) caused dose- and time-dependent pressor and bradycardic effect on cardiovascular system and increased respiratory rates, tidal volume and minute ventilation of normotensive rats. Also centrally injected CDP-choline accompanied by 62 % increase in extracellular total prostaglandin concentration in the posterior hypothalamus, as shown in microdialysis studies. Moreover, phospholipase A2 inhibitor mepacrine (250 µg; i.c.v.), phospholipase C inhibitor neomycine (250 µg; i.c.v.) and nonselective COX inhibitor ibuprofen (200 µg; i.c.v.) almost completely and thromboxane A2 synthesis inhibitor furegrelate (250 µg; i.c.v.) decreased CDP-cholineevoked cardiorespiratory effects. In conclusion, results show that centrally administered CDP-choline evokes pressor and bradycardic response on cardiovascular system and increases respiratory rates, tidal volume and minute ventilation in normotensive rats. Moreover, according to our findings, there is an involvement of the central prostaglandinergic system in CDP-choline-induced cardiorespiratory responses.
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Keywords
CDP-kolin, Prostaglandin sentezi, Fosfolipaz A2 – C, COX 1 – 2, Mikrodiyaliz, Kan basıncı, Kalp hızı, Tidal volüm, Dakika ventilasyon, Solunum sayısı, CDP-choline, Prostaglandin synthesis, Phopspholipase A2 – C, Microdialysis, Blood pressure, Heart rate, Tidal volume, Minute ventilation, Respiratory frequency
Citation
Topuz, B. B. (2013). CDP-kolin'in merkezi kardiyovasküler ve solunum düzenlenmesindeki rolü: Etkide merkezi prostaglandinerjik sistemin aracılığı. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.