The mechanism of serotonin induced biphasic effect on pulmonary vessels in the isolated perfused rat lungs

Year 2007, Volume: 9 Issue: 1, 27 - 35, 01.03.2007

Coskun Sılan Cihat Küçükhüseyın

Abstract

The aim of this work is detect to serotonin effect, serotonin lidoflazine interactions and possible mechanisms of these effect at isolated perfused rat pulmonary preparation. Lidoflazine, theophylline, methylene blue (MB) and cyproheptadine used in experiments. Lidoflazine is a calcium channel blocker, inhibits nucleoside transport and increase to endogenous adenosine. Theophylline antagonize to adenosine, methylene blue inhibits to guanylate cyclase. Our results show that serotonin caused a biphasic, dose related increase at pulmonary artery perfusion pressure. Early pressure response named as phase-I (F1) and late pressure response named as phase-II (F2). Lidofazine, causes a dose dependent increase at F1 and inhibition at F2. Cyproheptadine causes a dose related inhibition at both F1 and F2 serotonin responses. Our experiments show that, lidoflazine related potentiation of F1 was significantly antagonized by cyproheptadine. Lidoflazine-cyproheptadine combination significantly inhibits to F1 serotonin responses. Cyproheptadine potentiated to lidoflazine’s inhibitory effect to F2. Theophylline increased to F1 but this effect isn’t significant. Theophylline antagonized to lidoflazine’s potentiation of F1, nonsignificantly inhibited to F2 and potentiated to lidoflazine’s effect to this phase. MB inhibited both F1 and F2 and prevent from lidoflazine’s effect to F1. Due to serotonin responses are biphasic, different serotonin receptors may have at pulmonary vascular bed. Lidoflazine’s stimulant effect of F1 may have related to adenosine increas e. Due to F2 depression, lidoflazine may have nonspecific antagonistic effect to serotonin receptors which related to F2. Due to cyproheptadine’s inhibitory effect to F2 is stronger than F1, F1 may have related a different receptor compared to F2. Theophylline’s inhibition of lidoflazine’s F1 increases, indicate that adenosine have a role at this responses. MB experiments show that vascular endothelia have an important role at serotonin responses

Keywords

Lidoflazine, methylene blue, pulmonary vasoconstriction, serotonin, cyproheptadine

Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi.

Abstract

Bu çalismada izole perfüze siçan akciger preperatinda serotoninin etkileri, serotonin-lidoflazin etkilesmesi ve altta yatan olasi mekanizmalarin ortaya çikarilmasi amaçlanmistir. Deneylerde serotonin yanitlarina karsi nükleozid tranportunu inhibe ederek endojen adenozini arttiran ve kalsiyum kanal blokeri olan lidoflazin, adenozin antagonisti teofilin, guanilat -siklaz inhibitörü metilen-mavisi (MM) ve siproheptadin kullanilmistir. Sonuçlarimiz serotoninin pulmoner arter perfüzyon basincinda doza -bagimli bifazik bir artma yaptigini gösterdi. Erken pressör yanit faz-I (F1) ve bundan sonraki düsmeyi izleyen pressör yanit faz-II (F2) olarak isimlendirildi. Lidoflazin, serotonine bagli F1’de dozla orantili bir artma ve F2’de inhibisyon olusturdugu belirlendi. Siproheptadin ise; serotoninin hem F1‘de hemde F2 yanitlarinda doza bagli inhibisyon olusturdu. Deneylerimizde lidoflazinin F1’de yaptigi potansiyalizasyonun siproheptadin ile anlamli bir sekilde antagonize edildigi görüldü. Lidoflazin-siproheptadin kombinasyonu, serotoninin F1 yanitlarini anlamli bir sekilde deprese etti. Lidoflazinin F2’ye inhibitör etkisi siproheptadin ile potansiyelize edildi. Teofilin F1’de anlamli olmayan bir artma olusturdu ve lidoflazinin F1 yanitlarinda yaptigi potansiyalizasyonu antagonize etti; F2’de ise anlamli olmayan bir azalmaya neden oldu ve lidoflazinin bu faza olan inhibitör etkisini güçlendirdi. MM hem F1 hem de F2 de inhibitör etki yapti ve lidoflazinin F1 fazinda neden oldugu artmayi engelledi. Serotonin yanitlarinin bifazik olmasi siçan pulmoner vaskuler sistemde çesitli serotonin reseptörlerin bulundugunu düsündürmektedir. Lidoflazinin F1 arttirmasi, adenozini arttirmasi yoluyla olabilir. F2’nin deprese edilmesi, lidoflazinin F2’yi olusturan serotonin reseptörleri üzerine muhtemelen nonspesifik antagonistik etkisi oldugunu telkin etmektedir. Siproheptadinin F2 üzerine olan inhibitör etkisinin F1’den daha güçlü olmasi, F1’in F2’den daha farkli bir reseptör araciligi ile olusabilecegini düsündürmektedir. Teofilinin F1 yanitlarinda lidoflazinin yaptigi artisi inhibe etmesi, bu yanitta adenozinin rolü oldugunu akla getirmektedir. MM ile yapilan deneyler serotonin yanitlarinda damar endotelinin de önemli bir rol oynadigini göstermektedir

Keywords

Lidoflazin, Metilen Mavisi, Pulmoner Vazokonstriksiyon, Serotonin, Siproheptadin

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