Effect of MnSOD (E. coli) on the relaxation caused by sodium nitroprusside on isolated rat renal artery

Abstract

In this study themolecular foundation of nitric oxide induced relaxation of arteries, with or without endothelium, of normotensive and spontanously hypertensive ratswas re-examined. With this purpose in mind, the effects of the nitric oxide donor sodium nitroprusside (NaNP), with and without manganese containing superoxide dismutase (MnSOD E.C. 1.15.1.1), on rat renal artery relaxation was strudied. The results show that the relaxation effect of NaNP is two times higher in normotensive, compared to spontaneously hypertensive rats. Similar differences exist in the relaxation effects of NaNP on isolated renal arteries without endothelium, indicating that besides the difference in the function of an endothelium, concerning basal NO production in normotensive and hypertensive rats, there is a differencewith respect to NO relaxation in the smoothmuscle that is induced by hypertension. MnSOD decreased the relaxation effect of NaNP in all the examined renal arteries, more in normotensive than in hypertensive ones regardless of the presence of an endothelium. These results show that MnSOD, by modifying the chemical versatility of NO into redox active forms - nitrosonium (NO+) and nitroxyl (NO-), produces different relaxation effects in normotensive and hypertensive arteries of rats, with or without an endothelium, potentiating the role of nitroxyl induced relaxation in sponteneously hypertensive rats. The results prove the need for the synthesis of complex NO donors, as the mechanisms of artery relaxation are different due to an endothel and smooth mouscle changes in hypertensive, as compared to normotensive rats.

U ovom radu smo pokušali da detaljnije ispitamo molekulsku osnovu azotoksid indukovane relaksacije arterija, sa i bez endotela, normotenzivnih i spontano hipertenzivnih pacova. U tu svrhu ispitivan je efekat azot-oksid (NO) donora natrijum- nitroprusida (NaNP), bez i u prisustvu superoksid-dismutaze koja sadrži mangan (MnSOD, EC 1.15.1.1) na relaksaciju renalne arterije. Rezulati pokazuju dvostruko veći relaksantni efekat NaNP kod normotenzivnih, u odnosu na spontano hipertenzivne pacove. Slična razlika postoji i u relaksantnom efektu NaNP na izolovane renalne arterije normotenzivnog i hipertenzivnog pacova kada je odstranjen endotel što ukazuje da, pored razlike u funciji endotela u odnosu na bazalnu NO produkciju kod normotenzivnih i spontano hipertenzivnih pacova, postoje i promene u glatkim mišićima indukovane hipertenzijom, u odnosu na NO relaksaciju. MnSOD kod svih grupa smanjuje relaksantni efekat SNP i to više kod normotenzivnih nego kod hipertenzivnih nezavisno od prisustva endotela. Ovi rezultati pokazuju da MnSOD menjajući hemijsku prirodu iz NaNP oslobođenog NO u redoks aktivne forme – nitrozonijum (NO+) i nitroksil (NO–) – ostvaruje različit relaksantni efekat kod normotenzivnih i kod hiperetenzivnih pacova sa i bez endotela potencirajući značaj nitroksilom indukovane relaksacije kod spontano-hipertenzivnih pacova. Dobijeni rezultati potvrđuju potrebu sinteze NO donora koji daju različite redoks-aktivne forme NO budući da se primarni mehanismi relaksacije razlikuju u zavisnosti od karakteristika endotela i glatkih mišića, kod hipertenzije u odnosu na normotenzivno stanje.