The new NO donor Terpy induces similar relaxation in mesenteric resistance arteries of renal hypertensive and normotensive rats

Araújo, Alice V.; Pereira, Amanda C.; Grando, Marcella Daruge; Silva, Roberto Santana da; Bendhack, Lusiane Maria

doi:10.1016/j.niox.2013.08.001

Cited by 21 publications

(20 citation statements)

References 37 publications

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“…Besides the well-known effect of TERPY as a NO donor [7];[8];[9];[10]; [11], our work elucidates a secondary effect of TERPY as an eNOS activator and uncoupling factor. This effect of TERPY was associated with NO, ONOO–, and ROS production, BH 4 depletion, Cav-1-Tyr 14 phosphorylation and oligomer destabilization, and a decrease in Cav-1/eNOS interaction.…”

Section: Discussionmentioning

confidence: 69%

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Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

Potje

Chen

Oliveira

et al. 2017

Free Radical Biology and Medicine

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[Ru(terpy)(bdq)NO]3+ (TERPY) is a nitric oxide (NO) donor that promotes relaxation of the mesenteric artery and aorta in rats. We sought to investigate whether it acts as both an NO donor and endothelial NO synthase (eNOS) activator, as shown previously for nitroglycerin. Human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 cells transfected with empty vector (HEK) or eNOS cDNA (HEK-eNOS) were treated with TERPY (1 μM) for different lengths of time. eNOS expression, dimerization, and Ser1177 phosphorylation, caveolin-1 (Cav-1) oligomerization, Cav-1 Tyr14 phosphorylation were evaluated by Western blotting. Studies also assessed the production of reactive oxygen/nitrogen species (ROS/RNS) in HUVECs and HEK-eNOS cells. In HEK cells devoid of eNOS, TERPY released NO without additional stimulus indicating that is an NO donor. Moreover, in HEK-eNOS cells, TERPY-induced NO production that was blocked by L-NAME. In addition, TERPY increased ROS and ONOO– production which were blocked by more than 80% by BH4 (essential eNOS co-factor) and eNOS siRNA. These results suggest that TERPY-induced ROS and ONOO− production were originated from eNOS. HUVECs stimulated with TERPY showed increased eNOS Ser1177 and Cav-1 Tyr14 phosphorylation, and decreased eNOS dimerization, Cav-1 oligomerization, and Cav-1/eNOS interaction after 20 min. It suggests that TERPY induces eNOS hyperactivation and uncoupling by disrupting Cav-1/eNOS interaction and depleting BH4. Endothelium-dependent vasodilation in response to NO donor TERPY is associated with eNOS activation and uncoupling, and thereby appears to be mediated, at least in part, via eNOS-dependent ROS/RNS production.

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Section: Discussionmentioning

confidence: 69%

“…The TERPY-induced hypotensive effect is slow, long lasting, and it does not lead to reflex tachycardia [7]. Furthermore, TERPY promotes relaxation in aorta [7]; [9] and in resistance vessels [10] from hypertensive and normotensive rats.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

Potje

Chen

Oliveira

et al. 2017

Free Radical Biology and Medicine

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“…Bonaventura et al (2011), have shown that the K+ channels do not play important role in the relaxation induced by the NO donors in aortic rings from HT rats. In contrast, Araujo et al (2013) reported that the vascular relaxation induced by NO involves the activation of K+ channels sensitive to TEA in normotensive and renal hypertensive rat mesenteric resistance arteries.…”

Section: Discussionmentioning

confidence: 89%

Nitric Oxide Donor Dilates Aorta in Salt Loaded Rats via Activation of Inward-Rectifier Potassium Channels

Salihi

Shekha²,

Maulood³

et al. 2015

ZJPAS

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Since the mechanism of salt impairing NO-induced vascular relaxation is not fully clear, this study was designed to investigate the role of potassium (K +) channels in the vasodilatory effects of NO donor in salt loaded rats. Isolated thoracic aortic rings of adult male albino rats fed 8% NaCl containing diet for six weeks were used for isometric tension recording using PowerLab tissue bath system. The recorded data revealed that high salt diet (HS) did not change the relaxation responses to sodium nitroprusside (SNP, an NO donor) in rat's thoracic aortic rings. SNP-induced relaxation in salt loaded rats was significantly lower in rings contracted by high K + than phenylephrine (PE, a selective α1-adrenergic receptor agonist). On the other hand, incubation of aortic rings from salt loaded rats with inward-rectifier K + (K IR) channel blockers either individually or simultaneously with other K + channel blockers significantly inhibited SNP-induced relaxation in PE-contracted rings; however incubation of rings with either calcium (Ca +2)-activated K + (K Ca), ATP-dependent (K ATP) or voltage-sensitive K + (K V) channels blockers had non-significant effects on relaxation responses of SNP. These results reveal that NO donor-induced aortic relaxation from salt loaded rats is mainly mediated by the activation of K IR channels.

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“…TERPY induces similar vasodilator effects on endothelium-denuded (E − ) mesenteric artery rings of sham-operated (2K) and renal hypertensive (2K-1C) rats [20] and also on E − aortic rings of normotensive rats and SHR [8]. Nevertheless, endothelium modulates the TERPY vasodilator action in normotensive rats and SHR in different ways.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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We hypothesized that endothelium modulates relaxation induced by a nitric oxide (NO) donor ruthenium complex (TERPY, [Ru(terpy)(bdq)NO]) 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 Ser phosphorylation with consequent NO production and increased soluble guanylyl cyclase activity, which may have directly activated potassium channels.

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The new NO donor Terpy induces similar relaxation in mesenteric resistance arteries of renal hypertensive and normotensive rats

Cited by 21 publications

References 37 publications

Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

Nitric Oxide Donor Dilates Aorta in Salt Loaded Rats via Activation of Inward-Rectifier Potassium Channels

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

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