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

Published

Journal Article

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 Ser1177 phosphorylation with consequent NO production and increased soluble guanylyl cyclase activity, which may have directly activated potassium channels.

Full Text

Duke Authors

Cited Authors

  • Potje, SR; Troiano, JA; Grando, MD; Graton, ME; da Silva, RS; Bendhack, LM; Antoniali, C

Published Date

  • May 15, 2018

Published In

Volume / Issue

  • 201 /

Start / End Page

  • 130 - 140

PubMed ID

  • 29604271

Pubmed Central ID

  • 29604271

Electronic International Standard Serial Number (EISSN)

  • 1879-0631

Digital Object Identifier (DOI)

  • 10.1016/j.lfs.2018.03.055

Language

  • eng

Conference Location

  • Netherlands