Comparison of the mechanisms underlying the relaxation induced by two nitric oxide donors: Sodium nitroprusside and a new ruthenium complex

• DOI: 10.1016/j.vph.2006.10.002
• Publication Date: 2006-10-10T11:25:15Z
• Authors: Daniella Bonaventura; Renata Galvão de ...; Juliana A. Vercesi; Roberto Santana d...; Lusiane M. Bendhack
• Keywords: Male; Nitroprusside; 0301 basic medicine; Aorta, Thoracic; Free Radical Scavengers; In Vitro Techniques; Dinoprost; Rats; Norepinephrine; Phenylephrine; 03 medical and health sciences; Guanylate Cyclase; Oxyhemoglobins; Potassium Channel Blockers; Animals; Ruthenium Compounds; Nitric Oxide Donors; Cysteine; Endothelium, Vascular; Enzyme Inhibitors; Rats, Wistar; Cyclic GMP

We studied the mechanisms involved in the relaxation induced by nitric oxide (NO) donors, ruthenium complex ([Ru(terpy)(bdq)NO(+)](3+)-TERPY) and sodium nitroprusside (SNP) in denuded rat aorta. Both NO donors induced vascular relaxation independent of the agonist used in the pre-contraction. [Ru(terpy)(bdq)NO(+)](3+) and SNP activated guanylyl cyclase (GC) and K(+) channels. The production of cGMP induced by [Ru(terpy)(bdq)NO(+)](3+) - was higher than that obtained with SNP. The combination of GC inhibitor with K(+)channels blocker almost abolished the relaxation induced by the NO donors. The extracellular NO scavenger oxyhemoglobin reduced the potency without changing the maximum effect (Emax) of both NO donors. By using specific NO species scavengers, hydroxocobalamin and l-cysteine, we have identified the contribution of free radical NO (NO()) and nytroxil anion (NO(-)), respectively, to the rat aorta relaxation induced by both NO donors. The selective scavengers for NO() and NO(-) reduced the potency but not the Emax of [Ru(terpy)(bdq)NO(+)](3+). However, the NO(-) scavenger had no effect on the relaxation induced by SNP and NO() scavenger reduced only the potency to SNP. The inhibition of sarcoplasmic reticulum Ca(2+)-ATPase reduced only the potency of SNP without effect on the relaxation induced by [Ru(terpy)(bdq)NO(+)](3+). Our results demonstrate that both NO donors induce relaxation by activating the GC and K(+) channels. The NO() is the unique NO specie involved in the SNP-relaxation. On the other hand, the relaxant effect of [Ru(terpy)(bdq)NO(+)](3+) involves both NO() and NO(-), that produce higher concentration of cGMP. The inhibition of sarcoplasmic reticulum Ca(2+)-ATPase reduces the relaxation induced by SNP but it did not alter the relaxation induced by [Ru(terpy)(bdq)NO(+)](3+).