İzole tavşan böbreğinde, Endotelin 1`in böbrek perfüzyon basıncında, idrar hacminde ve böbrek ağırlığında oluşturduğu değişiklikler üzerinde stabil prostasiklin analoğu iloprostun etkisi ve bu etkide cAMP`nin rolü

Abstract

-44- 8.İNGİLİZCE ÖZET: Endothelin-1 (ET-1) and prostacyclin (PGI2) are the mediators, released from endothelium, cause an opposite effect on vascular smooth muscle. While ET-1 induces vasoconstriction, PGI2 causes vasodilatory effect. Therefore it can be assumed that there might be an interaction between these mediators. This study was undertaken to investigate the effect of lloprost (ILO), a stable analogue of PGI2, on the responses to ET-1 and the role of cAMP in this interaction in the isolated perfused rabbit kidney. ET-1 at the dose of 10`9 M caused an increase (9.86 ± 0.98 mmHg, n=13) and ILO (200 ng/ml) alone induced a decrease (2.29 ± 0.30 mmHg, n=13) in the perfusion pressure. ET-1 when used together with ILO causes an increase in perfussion pressure but this increase is found to be reduced when compared with ET-1 (4.94 ± 1.14 mmHg, n=13) (p<0.001). ET-1 caused an insignificant reduction in urine outflow. But ILO alone and ET-1+ILO together caused a significant reduction (p<0.05). Perfusion of ET-1, ILO and ET-1+ILO respectively caused a marked increase in kidney weights (before experiment: 13.57 ± 0.50 gr, after experiment: 14.99 ± 0.43 gr, n=5) (p<0.05). In perfusions of theophylline, ET-1, ILO or ET-1+ILO alone did not make any alteration in kidney weight. cAMP levels were found to be reduced in ET-1+ILO administered group (Control: 1300.67 ± 130.85 pmol/gr kidney, ET-1+ILO: 1114 ± 111.61 pmol/gr kidney, n=3) (p<0.05) while did not change in ET-1 or ILO alone applied groups. In conclusion; It was assumed that PGI2 plays a mediator role in response to ET-1 but cAMP as a second messenger didn't participitate this interaction.-43- cAMP ölçümlerinde ise ET-1, ILO uygulanan böbreklerle kontrol böbrekler arasında anlamlı bir konsatrasyon farkı gözlenmemiştir. ET-1+İLO uygulanan böbreklerde ise kontrollara göre azalmış olduğu görüldü (p<0.05). Sonuç olarak, ET'nin cevaplarında PGfe' nin mediator rol oynadığı fakat bu etkileşimde cAMP'nin aracılık etmediği düşünülmüştür.

-44- 8.İNGİLİZCE ÖZET: Endothelin-1 (ET-1) and prostacyclin (PGI2) are the mediators, released from endothelium, cause an opposite effect on vascular smooth muscle. While ET-1 induces vasoconstriction, PGI2 causes vasodilatory effect. Therefore it can be assumed that there might be an interaction between these mediators. This study was undertaken to investigate the effect of lloprost (ILO), a stable analogue of PGI2, on the responses to ET-1 and the role of cAMP in this interaction in the isolated perfused rabbit kidney. ET-1 at the dose of 10`9 M caused an increase (9.86 ± 0.98 mmHg, n=13) and ILO (200 ng/ml) alone induced a decrease (2.29 ± 0.30 mmHg, n=13) in the perfusion pressure. ET-1 when used together with ILO causes an increase in perfussion pressure but this increase is found to be reduced when compared with ET-1 (4.94 ± 1.14 mmHg, n=13) (p<0.001). ET-1 caused an insignificant reduction in urine outflow. But ILO alone and ET-1+ILO together caused a significant reduction (p<0.05). Perfusion of ET-1, ILO and ET-1+ILO respectively caused a marked increase in kidney weights (before experiment: 13.57 ± 0.50 gr, after experiment: 14.99 ± 0.43 gr, n=5) (p<0.05). In perfusions of theophylline, ET-1, ILO or ET-1+ILO alone did not make any alteration in kidney weight. cAMP levels were found to be reduced in ET-1+ILO administered group (Control: 1300.67 ± 130.85 pmol/gr kidney, ET-1+ILO: 1114 ± 111.61 pmol/gr kidney, n=3) (p<0.05) while did not change in ET-1 or ILO alone applied groups. In conclusion; It was assumed that PGI2 plays a mediator role in response to ET-1 but cAMP as a second messenger didn't participitate this interaction.