Upregulation of endothelium-derived hyperpolarizing factor compensates for the loss of nitric oxide in mesenteric arteries of dahl salt-sensitive hypertensive rats

Gotō, Kenichi; Kansui, Yasuo; Oniki, Hideyuki; Ohtsubo, Toshio; Matsumura, Kiyoshi; Kitazono, Takanari

doi:10.1038/hr.2012.36

Cited by 28 publications

(25 citation statements)

References 47 publications

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“…The vascular strain governed by smooth muscle cells in the small arteries plays important roles in the formation and elevation of BP [19]. Most previous studies that explored vascular function were performed in vitro and mainly used isolated aortas or distributing arteries [20, 21]. However, the main artery and the distributing arteries play a much smaller role in maintaining peripheral vascular resistance when compared with the small arteries.…”

Section: Discussionmentioning

confidence: 99%

High Sodium Intake Impairs Small Artery Vasoreactivity in vivo in Dahl Salt-Sensitive Rats

Wang

Chen

et al. 2019

J Vasc Res

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The effects of high sodium intake on the functionality of resistance arteries have been repeatedly studied in vitro, but no study has focused on salt-sensitive hypertension in vivo. We studied the in vivo reactivity of mesenteric small arteries (MSAs) to vasoactive agents in Dahl salt-sensitive (DS) rats with various sodium diets. Twenty-four male DS rats were randomized into 3 groups: LS (0.3% NaCl diet), NS (0.6% NaCl diet), and HS (8% NaCl diet). After a 12-week intervention, the diameter changes of the MSAs after noradrenaline (NA) and acetylcholine (ACh) exposure were detected by a microscope, and changes in blood perfusion through the MSAs were measured by full-field laser perfusion imaging. HS enhanced the constrictive response of the MSAs to NA and attenuated the relaxing response to ACh. Low sodium intake reduced the response of the MSAs to NA and promoted ACh-induced vasodilatation. HS also aggravated NA-induced blood perfusion reduction and impaired ACh-induced hyperperfusion of the MSAs. Pathologically, HS was associated with arteriolar structural damage and fibrosis of the MSAs. We conclude that sodium intake affects the responsiveness of the MSAs to vasoactive agents in DS rats and might play important roles in modulating blood pressure in hypertensive individuals.

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Section: Discussionmentioning

confidence: 99%

High Sodium Intake Impairs Small Artery Vasoreactivity in vivo in Dahl Salt-Sensitive Rats

Wang

Chen

et al. 2019

J Vasc Res

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“…In coronary artery disease, compensation occurs via increased K ϩ channel activity and increased release of hyperpolarizing factors (30), while in hypercholesterolemia, compensatory increases in Ca 2ϩ -dependent K ϩ channels is evident (31). EDHF has also been shown to compensate for diminished nitric oxide-dependent dilation in numerous disease states, including type 2 diabetes (36), hypertension (14), and hyperparathyroidism (45).…”

Section: Discussionmentioning

confidence: 99%

“…A primary feature of endothelial dysfunction is the inability of arteries and arterioles to dilate fully in response to vasoactive agonists (11). However, other vasodilatory pathways have been shown to be augmented in conditions in which nitric oxide availability is reduced (3,14,30,36). This redundancy in vasodilator signaling pathways allows for compensation if one mechanism is impaired.…”

mentioning

confidence: 99%

Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts

Deer

Heaps

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Deer RR, Heaps CL. Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts. Am J Physiol Heart Circ Physiol 305: H1321-H1331, 2013. First published August 30, 2013; doi:10.1152/ajpheart.00531.2013.-Exercise training of coronary artery disease patients is of considerable interest, since it has been shown to improve vascular function and, thereby, enhance blood flow into compromised myocardial regions. However, the mechanisms underlying exercise-induced improvements in vascular function have not been fully elucidated. We tested the hypothesis that exercise training increases the contribution of multiple mediators to endothelium-dependent relaxation of coronary arteries in the underlying setting of chronic coronary artery occlusion. To induce gradual occlusion, an ameroid constrictor was placed around the proximal left circumflex coronary artery in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary or exercise (treadmill, 5 days/wk) regimens for 14 wk. Exercise training significantly enhanced the contribution of nitric oxide, prostanoids, and large-conductance Ca 2ϩ -dependent K ϩ (BKCa) channels to endothelium-dependent, bradykinin-mediated relaxation in nonoccluded and collateral-dependent arteries. Combined nitric oxide synthase, prostanoid, and BK Ca channel inhibition ablated the enhanced relaxation associated with exercise training. Exercise training significantly increased nitric oxide levels in response to bradykinin in endothelial cells isolated from nonoccluded and collateral-dependent arteries. Bradykinin treatment significantly increased PGI 2 levels in all artery treatment groups and tended to be further enhanced after nitric oxide synthase inhibition in exercise-trained pigs. No differences were found in whole cell BK Ca channel currents, BKCa channel protein levels, or arterial cyclic nucleotide levels. Although redundant, upregulation of parallel vasodilator pathways appears to contribute to enhanced endothelium-dependent relaxation, potentially providing a more refined control of blood flow after exercise training. exercise; endothelium; chronic coronary artery occlusion THE ENDOTHELIUM PLAYS AN IMPORTANT role in mediating vascular tone. In response to mechanical stimuli (shear stress and pulsatile pressure) or vasoactive agonists (bradykinin and acetylcholine), endothelium-dependent relaxation occurs through the release of mediators such as nitric oxide and PGI 2 , which affect the adjacent vascular smooth muscle in a paracrine manner. In addition, a third endothelium-derived factor [endothelium-derived hyperpolarizing factor (EDHF)] relaxes vascular smooth muscle by causing hyperpolarization of the underlying smooth muscle cells. While a single EDHF has not been elucidated, numerous candidate mechanisms or pathways have been proposed. Large-conductance Ca 2ϩ -dependent K ϩ (BK Ca ) channels are a common downstream effector for several of these potential EDHFs (2, 27), as well as for nitric oxide (29) and PGI 2 ...

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“…Considering that the L -NA-resistant vasorelaxation to ACh seemed to be subtly augmented while the response to SNP was unaffected under hypoxia for 3 h, endothelium-derived relaxing factors other than NO, such as prostacyclin and endothelium-derived hyperpolarizing factor, may compensate for the decrease in endothelial NO bioavailability. In fact, accumulating evidence has shown that these mediators act as backup mechanism to preserve endothelium-derived vasodilator regulation of mesenteric arterial tone in several disease models, including hypertension [21,22] and diabetes [23]. Unfortunately, there is no evidence that this phenomenon quickly occurs within hours when the bioavailability of NO is impaired, so further study is required to establish this indication.…”

Section: Discussionmentioning

confidence: 99%

Influence of Hypoxia on Endothelium-Derived NO-Mediated Relaxation in Rat Carotid, Mesenteric and Iliac Arteries

Tawa

Shimosato²,

Geddawy³

et al. 2013

Pharmacology

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Individual vascular beds exhibit differences in vascular reactivity. The present study examined the influence of hypoxia on endothelium-dependent, especially nitric oxide (NO)-mediated, relaxation in the isolated rat common carotid, superior mesenteric and external iliac arteries. Hypoxia for 1 and 3 h had no effects on the relaxations caused by acetylcholine (ACh) and sodium nitroprusside (SNP) in common carotid and external iliac arteries. In addition, NO synthase inhibitor N^G-nitro-L-arginine (L-NA, 10 μmol/l)-resistant, endothelium-dependent relaxations by ACh were also unaffected by hypoxia in these arteries. On the other hand, ACh-induced relaxation in superior mesenteric arteries was significantly impaired by exposure to hypoxia, while this condition did not affect the relaxation induced by SNP or ACh in the presence of L-NA. This impairment was partially prevented by treatment with tempol (3 mmol/l), a superoxide scavenger. These findings demonstrate a marked heterogeneity in response to hypoxia in rat arteries. Briefly, acute hypoxia induces impairment of endothelium-derived NO-mediated relaxation through the decrease in its bioavailability in the superior mesenteric, but not in common carotid or external iliac, arteries. Furthermore, superoxide seems to be one causal factor responsible for the undesirable effect of hypoxia.

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Upregulation of endothelium-derived hyperpolarizing factor compensates for the loss of nitric oxide in mesenteric arteries of dahl salt-sensitive hypertensive rats

Cited by 28 publications

References 47 publications

High Sodium Intake Impairs Small Artery Vasoreactivity in vivo in Dahl Salt-Sensitive Rats

High Sodium Intake Impairs Small Artery Vasoreactivity in vivo in Dahl Salt-Sensitive Rats

Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts

Influence of Hypoxia on Endothelium-Derived NO-Mediated Relaxation in Rat Carotid, Mesenteric and Iliac Arteries

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