Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta.
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 AuNPs-{Ru-4PySH}n is lower than Ru-4PySH. Both complexes release only NO(0) specie, but AuNPs-{Ru-4PySH}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. Non-selective potassium (K(+)) channel blocker TEA had no effect on the vasodilation induced by AuNPs-{Ru-4PySH}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.
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, SP 14049-900 Brazil ; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, SP 14040-903 Brazil ; 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.
Bruno R
BR
Silva
Faculty of Ceilândia, University of Brasilia, Brasília, DF 7220-140 Brazil.
Claure N
CN
Lunardi
Institute of Chemistry, University of São Paulo, São Paulo, SP 05508-000 Brazil.
Koiti
K
Araki
Laboratory of Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, SP 14040-903 Brazil.
Juliana C
JC
Biazzotto
Laboratory of Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, SP 14040-903 Brazil.
Roberto S
RS
Da Silva
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, SP 14040-903 Brazil.
Lusiane M
LM
Bendhack
Gold nanoparticle; NO donor ruthenium complex; Nitric oxide (NO); Potassium channels; Soluble guanylyl cyclase; Vasodilation