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

Author:
Potje, Simone R., Troiano, Jéssica A., Grando, Marcella D., Graton, Murilo E., da Silva, Roberto S., Bendhack, Lusiane M., Antoniali, Cristina
Source:
Life sciences 2018 v.201 pp. 130-140
ISSN:
0024-3205
Subject:
animal disease models, endothelial nitric oxide synthase, endothelium, enzyme activity, guanylate cyclase, hypertension, mesenteric arteries, nitric oxide, phosphorylation, potassium channels, rats, ruthenium, tetraethylammonium compounds
Abstract:
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.
Agid:
5929590