Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats

Autor(es)

Potje, Simone R. ^[1] ; Troiano, Jessica A. ^[1] ; Grando, Marcella D. ^[2] ; Graton, Murilo E. ^[1] ; da Silva, Roberto S. ^[2] ; Bendhack, Lusiane M. ^[2] ; Antoniali, Cristina ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, UNESP, Programa Multicentr Posgrad Ciencias Fisiol SBFis, Sch Dent, Dept Basic Sci, Aracatuba - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 201, p. 130-140, MAY 15 2018.
• Citações Web of Science: 0

Resumo

We hypothesized that endothelium modulates relaxation induced by a nitric oxide (NO) donor ruthenium complex (TERPY, {[}Ru(terpy)(bdq)NO](3+)) in mesenteric arteries of normotensive and spontaneously hypertensive (SHR) rats in different ways. We analyzed the mechanism involved in TERPY-induced relaxation in the second and third branches of mesenteric arteries and investigated how endothelium contributes to the TERPY vasodilator effect on SHR blood vessels. TERPY induced concentration-dependent relaxation in endothelium-denuded (E-) and endothelium-intact (E-) mesenteric arteries of normotensive rats and SHR. Pretreatment with ODQ (which inhibits soluble guanylyl cyclase) or TEA (tetraethylammonium, which blocks potassium channels) significantly reduced the TERPY vasodilator effect on E+ mesenteric arteries of normotensive rats and SHR. The presence of endothelium shifted the concentration-effect curves for TERPY in E- mesenteric arteries of normotensive rats to the right. Conversely, the presence of endothelium shifted the concentration-effect curves for TERPY in the case of SHR E- mesenteric arteries to the left, which suggested increased potency. L-NNA, a more selective endothelial NO synthase (eNOS) inhibitor, reduced TERPY potency in SHR. The presence of endothelium and notably of NOS contributed to the TERPY vasodilator action in SHR: TERPY promoted eNOS phosphorylation with consequent NO production and increased soluble guanylyl cyclase activity, which may have directly activated potassium channels. (AU)

• Processo FAPESP: 15/17080-2 - Efeitos do estiramento sobre a vasoconstrição modulada pelo endotélio em aorta e coronária de ratos hipertensos renais
• Beneficiário: Lusiane Maria Bendhack
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/20398-6 - Participação da via PI3-K/Akt/NOSe, glicosaminação (O-GlcNAc) e EROs na hiporeatividade vascular e hipotensão observada ao final da prenhez de ratas normotensas e espontaneamente hipertensas (SHR)
• Beneficiário: Cristina Antoniali Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/20998-0 - Análise in vivo e in vitro do efeito da apocinina sobre a disfunção endotelial de ratos espontaneamente hipertensos (SHR)
• Beneficiário: Cristina Antoniali Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular