Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta
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ORIGINAL ARTICLE
Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta Bruno R. Silva & Claure N. Lunardi & Koiti Araki & Juliana C. Biazzotto & Roberto S. Da Silva & Lusiane M. Bendhack
Received: 16 January 2014 / Accepted: 4 March 2014 / Published online: 23 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Nitric oxide (NO) plays an important role on several biological functions. Recently, it has been reported the possibility of modifying the NO release profile from the NO donors through its coupling to gold nanoparticles (AuNPs). Thus, AuNPs were synthesized and they were exposed to the NO donor ruthenium complex Cis-[Ru(bpy) 2 (NO)(4PySH)].(PF6) 3 termed (Ru-4PySH)—forming AuNPs-{Ru-4PySH} n cluster. Our results indicate that AuNPs do not modify the maximum effect (ME) and potency (pD2) in the vasodilation induced by Ru-4PySH. Both complexes induce similar vascular relaxation in concentration-dependent way. However, the NO released from the complex B. R. Silva Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo SP 14049-900, Brazil C. N. Lunardi Faculty of Ceilândia, University of Brasilia, Brasília DF 7220-140, Brazil K. Araki Institute of Chemistry, University of São Paulo, São Paulo SP 05508-000, Brazil J. C. Biazzotto : R. S. Da Silva Laboratory of Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo SP 14040-903, Brazil B. R. Silva : L. M. Bendhack Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo SP 14040-903, Brazil B. R. Silva (*) Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café S/N, 14040-903 Ribeirão Preto, São Paulo, Brazil e-mail: [email protected]
AuNPs-{Ru-4PySH}n is lower than Ru-4PySH. Both complexes release only NO0 specie, but AuNPs-{Ru4PySH}n releases NO in constant way and exclusively in the extracellular medium. In time-course, Ru-4Py-SH was faster than AuNPs-{Ru-4PySH}n in inducing the maximum vasodilation. Inhibition of soluble guanylyl cyclase (sGC) abolished the vasodilation induced by Ru-4PYSH, but not by AuNPs-{Ru-4PySH} n . Nonselective potassium (K+) channel blocker TEA had no effect on the vasodilation induced by AuNPs-{Ru4PySH}n, but it reduced the potency to Ru-4PySH. In conclusion, our results suggest that AuNPs can reduce the permeability of NO donor Ru-4PySH due to AuNPs-{Ru-4PySH}n cluster formation. AuNPs reduce NO release, but they do not impair the vasodilator effect induced by the NO donor. Ru-4PySH induces vasodilation by sGC and K+ channels activation, while AuNPs-{Ru-4PySH}n activates mainly sGC. Taken together, these findings represent a new pharmacological strategy to control the NO release which could activate selective biological targets. Keywords Gold nanoparticle . Vasodilation . Nitric oxide (NO) . NO donor ruthenium complex . Soluble guanylyl cyclase . Potassium channels
Introducti
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