METEHAN UZUN, MEHMET ÇİTİL, ONUR ATAKİŞİ, Edoğan UZLU, Kürşat YAPAR, HİDAYET METİN ERDOĞAN

Plasma nitric oxide levels after injection of therapeutic dose of methylprednisolone acetate in rabbits

Metil prednizolon asetat (MPA) sentetik glukokortikoitler (GC) grubuna üye önemli ve uzun etkili bir ajandır. Diğer bir sentetik GC olan dekzametazonun nitrik oksit (NO) sentezi üzerine olan baskılayıcı etkisi çok iyi bilinmesine rağmen MPA’nın etkisi tam olarak ortaya konulmamıştır. Bu araştırma ile sağlıklı tavşanlara tedavi dozlarında uygulanan MPA (depo-medrol)’nın enjeksiyon öncesi ve enjeksiyon sonrası 1, 4 ve 7. günlerdeki kan NO düzeylerindeki değişimlerin belirlenmesi amaçlanmıştır. Araştırmada iki farklı deney grubu oluşturulmuş ve 2.5 (Grup I, n=6) ve 5.0 (Grup II, n=7) mg/kg MPA kas içi enjekte edilmiştir. Enjeksiyon öncesi (0. gün) ve enjeksiyon sonrası 1, 4 ve 7. günlerde kulak venasından alınan kan örneklerinde NO düzeyleri belirlenmiştir. MPA uygulaması sonrası her iki grupta da 4. günde NO düzeylerinin daha düşük olduğu belirlenmiştir (P

Anahtar Kelimeler:

glukokortikoidler, tavşan, nitrik oksit, kortikoidler, kan basıncı

Tavşanlarda tedavi dozunda metilprednizolon asetat enjeksiyonunu sonrası plazma nitrik oksit düzeyleri

The methylprednisolone asetate (MPA) is an important and long acting member of synthetic glucocorticoids (GC). Although the suppressive effect of GC especially dexamethasone on nitric oxide (NO) synthesis is well known, the effect of MPA on NO production is not fully documented. This study evaluated changes in plasma NO levels before and on day 1, 4 and 7 after injection of two different therapeutic dose of methylprednisolone asetate (MPA; Depo-medrol) in healthy rabbits. The MPA was injected intramuscularly at 2.5 (Group I, n=6) and 5.0 (Group II, n=7) mg/kg doses. Blood samples were collected from auricular vein before and on day 1, 4 and 7 after injections and the NO levels were determined. MPA treatment decreased NO values on day 4 (P<0.001) in both groups. In conclusion, the role of therapeutic dose of long acting MPA administration on the decreased plasma NO levels should be considered by clinicians.

Keywords:

glucocorticoids, rabbits, nitric oxide, corticoids, blood pressure,

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Leclercq B, Jaimes EA, Raij L: Nitric oxide synthase and hypertension. Curr Opin Nephrol Hypertens, 11 (2): 185-189, 2002.
Johns D G, Dorrance AM, Tramontini NL, Webb RC: Glucocorticoids inhibit tetrahydrobiopterin dependent endothelial function. Exp Biol Med, 226 (1): 27-31, 2001.
Schäfer SC, Wallerath T, Closs EI, Schmidt C, Schwarz PM, Förstermann U, Lehr HA: Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Am J Physiol Heart Circ Physiol, 288 (1): H436-444, 2005.
Wallerath T, Witte K, Schäfer SC, Schwarz PM, Prellwitz W, Wohlfart P, Kleinert H, Lehr HA, Lemmer B, Förstermann U: Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci, 96 (23): 13357-13362, 1999.
Muzaffar S, Shukla N, Srivastava A, Angelini GD, Jeremy JY: Sildenafil citrate and sildenafil nitrate (NCX 911) are potent inhibitors of superoxide formation and gp91phox expression in porcine pulmonary artery endothelial cells. Br J Pharmacol, 146 (1): 109-117, 2005.
Whitworth JA, Schyvens CG, Zhang Y, Andrews MC, Mangos GJ, Kelly JJ: The nitric oxide system in glucocorticoid-induced hypertension. J Hypertens, 20 (6): 1035-1043, 2002.
Ungemach FR: Pharmaka zur Beeinflussung von Entzündungen. In, Löscher W, Ungemach FR, Kroker R (Eds): Grundlagen der Pharmakotherapie bei Haus-und Nutztieren. 325-322, Verlag Paul Parey, Berlin und Hamburg, 1994.
Miranda KM, Espey MG, Wink DA: A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 5 (1): 62-71, 2001.
Mitchell BM, Webb RC: Impaired vasodilation and nitric oxide synthase activity in glucocorticoid-induced hypertension. Biol Res Nurs, 4 (1): 16-21, 2002.