Artículos de revistas
In Vivo Effects Of The Controlled No Donor/scavenger Ruthenium Cyclam Complexes On Blood Pressure
Registro en:
Life Sciences. , v. 70, n. 23, p. 2735 - 2752, 2002.
243205
10.1016/S0024-3205(02)01528-X
2-s2.0-0037177476
Autor
Marcondes F.G.
Ferro A.A.
Souza-Torsoni A.
Sumitani M.
Clarke M.J.
Franco D.W.
Tfouni E.
Krieger M.H.
Institución
Resumen
Ruthenium(II/III) complexes able to bind and release NO • were tested in vivo, in conscious Wistar rats instrumented for continuous blood pressure (BP) measurement and administration of in bolus injections (5 to 100 nmol/Kg i.v.) of trans-[Ru IICl(NO +)(cyclam)](PF 6) 2 (cyclam-NO) or sodium nitroprusside (SNP). For normotensive rats, cyclam-NO produced a sustained 10% BP reduction of basal MAP during 7 ± 0.4 to 11 ± 0.3 min. In acute hypertensive rats, cyclam-NO produced BP reduction 3-fold larger than in normotensive rats and similar to that of SNP (maximal effect: 41 ± 1.3 vs. 45 ± 2.2 mmHg, respectively). However, the duration of the effect of cyclam-NO was 13 to 21-fold longer than that of SNP. The hypotensive effect of cyclam-NO was fully blocked in presence of continuous infusion of a NO • scavenger, carboxy-PTIO (6 mmol/Kg/min), or of the inhibitor of cGMP activation, methylene blue (83 nmol/Kg/min), or of the cyclam-NO precursor, trans-[RuCl(tfms)(cyclam)](tfms) (cyclam-tfms) (500 mmol/Kg/min). The long lasting BP reduction of cyclam-NO can be interpreted in terms of a slower rate of NO • release (k -NO = 2.2 × 10 -3 s -1 at 35°C) following chemical reduction (E 0′ = 0.10 V vs NHE). In summary, cyclam-NO showed an hypotensive effect around 20 times longer than SNP in either normotensive or hypertensive rats, which was completely inhibited by methylene blue or carboxy-PTIO. Continuous infusion of cyclam-tfms completely blocked the hypotensive effect of cyclam-NO by scavenging the NO • released by the reduced cyclam-NO. © 2002 Elsevier Science Inc. 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