L omega -nitro-L-arginin-metil esterin (L-NAME) ile kronik nitrik oksit sentaz enzim inhibisyonu yapılan sıçanlarda kalp iskemi-reperfüzyon aritmileri ve endojen antioksidan enzimlerin etkinliğinin incelenmesi

Abstract

6. Özet Miyokardiyal iskemiyi takiben gerçekleşen reperfuzyona bağlı olarak ciddi aritmilerin çıktığı bilinmektedir. Nitrik oksidin de iskemi-reperfuzyon hasarında rol oynadığım bildiren çalışmalar vardır. Değişik in vivo modellerde kronik nitrik oksit sentaz inhibisyonu yapmak için L-NAME kullanılmaktadır. Bu çalışmada nitrik oksit sentaz enziminin kronik inhibisyonunun, erkek ve dişi sıçanlarda iskemi-reperfuzyon aritmilerine ve antioksidan enzimlere olan etkisinin incelenmesi amaçlanmıştır. Bu amaçla erkek ve dişi sıçanlar dörder gruba ayrıldı. L-NAME çeşme suyu içerisinde 15 gün süreyle, bir gruba 100 mg/1, diğer gruba 500 mg/1 olacak şekilde verildi. Kontrol gruplarına ise yalnızca çeşme suyu verildi. Her iki cinsiyet için birer sham öpere grubu biyokimyasal sonuçların karşılaştırılması için oluşturuldu. Deney esnasında, sol ana koroner artere, 7 dakika oklüzyon, 7 dakika reperfuzyon uygulanarak, ortaya çıkan aritmiler değerlendirildi. Sham öpere gruplara I/R yapılmadan sadece cerrahi işlem yapıldı. İskemi öncesi kan basıncı ortalamalarında L-NAME verilen gruplarda, hem erkek, hem dişilerde, kontrole göre anlamlı artış tespit edildi. Yalnızca çeşme suyu verilen gruplarda, dişi sıçanlardaki VEB sayılan, VT ve VF süreleri, erkek sıçanlara göre anlamlı olarak yüksek bulundu. Kronik L-NAME uygulanması erkek sıçanlardaki VEB sayıları, VT ve VT+VF sürelerinde artışa neden olurken, dişi sıçanlarda oluşan aritmilerde anlamlı bir değişikliğe neden olmadı. Erkek I/R yapılan gruplarda sham öpere gruba göre artmış NO düzeyi tesbit edildi. Dişi I/R yapılan gruplarda sham öpere gruba göre CAT aktivitelerinde artış, GSH-Px aktivitelerinde azalma gözlemlendi. MDA düzeylerinde II/R uygulanan gruplarda beklenen artış izlenmedi. Enzim çalışmalarında elektrofizyolojik sonuçlar gibi kalpte I/R hasarında erkek ve dişilerde farklı mekanizmalrm yer alabileceğini düşündürmektedir. Bu bulgular, nitrik oksidin iskemi-reperfuzyon 82aritmilerindeki rolünün cinsiyete göre değişebileceğini ve erkek sıçanlarda koruyucu rolü olabileceğini düşündürmektedir. Abstract Serious arrhythmias has been known to occur on reperfusion after myocardial ischemia. Some studies showed that nitric oxide (NO) had a role on ischaemia- reperfusion injury. N^-nitro-L-arginine metyl ester (L-NAME) has been used to inhibit nitric oxide synthase (NOS) chronically in different in vivo models. The aim of this study was to investigate the effects of chronic nitric oxide synthase inhibition on ischemia- reperfusion arrhythmias and antioxidant enzymes in male and female rats. Male and female rats were divided into four groups. L-NAME was given as 100 mg/L or 500 mg/L in tap water for 15 days. Only tap water was given in control group. Shame opere groups were designed to compare biochemical results for both male and female rats. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Surgical procedure were applied to shame opere groups without I/R procedures. Mean blood pressure values before ischemia were higher in L-NAME groups than control groups in both male and female rats. For control groups, VEB numbers, VT and VF durations were higher in female rats than male rats. Chronic L-NAME administration increased the VEB numbers, VT and VT+VF durations in male rats but had no effect on arrhythmias in female rats. There was an increased NO levels in I/R performed male groups than shame opere one. CAT activities of I/R performed female rats were rised than shame opere ones and GSH-Px activities were decreased in I/R performed female groups than in shame group. MDA levels were not increased unexpectedly in I/R groups of both sexes. As electrophysiological studies, the enzyme results showed that I/R injury in heart could have different mechanism in male and female groups. These results suggest that the role of nitric oxide on ischaemia-reperfusion 83

aritmilerindeki rolünün cinsiyete göre değişebileceğini ve erkek sıçanlarda koruyucu rolü olabileceğini düşündürmektedir. Abstract Serious arrhythmias has been known to occur on reperfusion after myocardial ischemia. Some studies showed that nitric oxide (NO) had a role on ischaemia- reperfusion injury. N^-nitro-L-arginine metyl ester (L-NAME) has been used to inhibit nitric oxide synthase (NOS) chronically in different in vivo models. The aim of this study was to investigate the effects of chronic nitric oxide synthase inhibition on ischemia- reperfusion arrhythmias and antioxidant enzymes in male and female rats. Male and female rats were divided into four groups. L-NAME was given as 100 mg/L or 500 mg/L in tap water for 15 days. Only tap water was given in control group. Shame opere groups were designed to compare biochemical results for both male and female rats. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Surgical procedure were applied to shame opere groups without I/R procedures. Mean blood pressure values before ischemia were higher in L-NAME groups than control groups in both male and female rats. For control groups, VEB numbers, VT and VF durations were higher in female rats than male rats. Chronic L-NAME administration increased the VEB numbers, VT and VT+VF durations in male rats but had no effect on arrhythmias in female rats. There was an increased NO levels in I/R performed male groups than shame opere one. CAT activities of I/R performed female rats were rised than shame opere ones and GSH-Px activities were decreased in I/R performed female groups than in shame group. MDA levels were not increased unexpectedly in I/R groups of both sexes. As electrophysiological studies, the enzyme results showed that I/R injury in heart could have different mechanism in male and female groups. These results suggest that the role of nitric oxide on ischaemia-reperfusion 83arrhythmias may be different according to sex and nitric oxide may have a protective effect on these arrhythmias in male rats. 84