New No Donor Inhibits Contraction Of Smooth Muscle Cell Through Activation Of Guanylyl-Cyclase And Sarcoplasmic Reticulum Ca+2-Atpase (Serca).

This study aimed to investigate the pathways involved in the vasodilatation induced by the new NO donor cis-[Ru(bpy)2(py)(NO2)](PF6)3 (PY) synthesized in our laboratory. Vascular reactivity to PY was studied in denuded rat aorta pre-contracted with phenylephrine (Phe) or 60mM KCl. Concentration-effect curves for PY were constructed in the presence or in the absence of the selective inhibitor of soluble guanylyl- cyclase (sGC) (ODQ), superoxide scavenger (Tiron) and SERCA inhibitor (Thapsigargin, TG). It was also constructed concentration-effect curves for CaCl2 under stimulation with 100nM Phe with or without PY. NO was released by the compound only in presence of the aortic tissue as detected by amperometry with a selective sensor. The NO donor reached the maximum aortic rings relaxation (ME) in 210 seconds. PY induced complete relaxation of the aortic rings pre-contracted with Phe or KCl in a concentration-dependent way but the ME and potency (pD2) values were lower in KCl than in Phe-contracted aorta. These responses were inhibited by ODQ and TG. The contractions to increased concentrations of extracellular Ca2+ were abolished by the 3 uM PY. The effect of PY was blocked by ODQ or TG. Our results show that the NO released from PY in the tissue induces relaxation due to the activation of the enzymes sGC and SERCA. It also inhibits Ca2+ influx and consequent contractile response. Financial Support: Fapesp and CNPq.