Attenuation of conducted vasodilatation in rat mesenteric arteries during hypertension: role of inwardly rectifying potassium channels

Gotō, Kenichi; Rummery, Nicole M.; Grayson, T. Hilton; Hill, Caryl E.

doi:10.1113/jphysiol.2004.070458

Cited by 82 publications

(120 citation statements)

References 46 publications

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“…In previous studies using rat mesenteric arteries under transient stimulation, conduction of the acetylcholine response was shown to reach up to 2000 μm 33, 34. We now show that this response is sustained that the sustained response is concentration‐dependent and well fitted by an exponential decay in accordance with the above studies.…”

Section: Discussionsupporting

confidence: 90%

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two‐compartment in vitro set‐up

et al. 2018

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AimConduction of vasomotor responses may contribute to long‐term regulation of resistance artery function and structure. Most previous studies have addressed conduction of vasoactivity only during very brief stimulations. We developed a novel set‐up that allows the local pharmacological stimulation of arteries in vitro for extended periods of time and studied the conduction of vasomotor responses in rat mesenteric arteries under those conditions.MethodsThe new in vitro set‐up was based on the pressure myograph. The superfusion chamber was divided halfway along the vessel into two compartments, allowing an independent superfusion of the arterial segment in each compartment. Local and remote cumulative concentration‐response curves were obtained for a range of vasoactive agents. Additional experiments were performed with the gap junction inhibitor 18β‐glycyrrhetinic acid and in absence of the endothelium.ResultsPhenylephrine‐induced constriction and acetylcholine‐induced dilation were conducted over a measured distance up to 2.84 mm, and this conduction was maintained for 5 minutes. Conduction of acetylcholine‐induced dilation was inhibited by 18β‐glycyrrhetinic acid, and conduction of phenylephrine‐induced constriction was abolished in absence of the endothelium. Constriction in response to high K+ was not conducted. Absence of remote stimulation dampened the local response to phenylephrine.ConclusionThis study demonstrates maintained conduction of vasoactive responses to physiological agonists in rat mesenteric small arteries likely via gap junctions and endothelial cells, providing a possible mechanism for the sustained functional and structural control of arterial networks.

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Section: Discussionsupporting

confidence: 90%

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two‐compartment in vitro set‐up

et al. 2018

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“…There was a loss of the K ϩ channel pathway in small arteries from hypertensive rats, which is consistent with previous reports in small mesenteric arteries in SHR and ANG rats. 10,[31][32][33][34][35] Studies that have assessed EDHF-and NOS-mediated dilation in mesenteric resistance arteries from hypertensive rats and mice report decreased NO and/or EDHF contributions to relaxation in mesenteric arteries. 12,[32][33][34][35] Although it is very difficult to compare these studies because of differences in experimental protocols and/or animal models, many of these studies observed an imbalance of the EDHF and/or NOS pathways in the vasodilator response.…”

Section: Endothelial Dysfunction In Large and Small Arteries Is Distinctmentioning

confidence: 99%

Novel Nitric Oxide Synthase–Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats

et al. 2007

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Abstract-To determine the mechanism(s) involved in vasorelaxation of small arteries from hypertensive rats, normotensive (NORM), angiotensin II-infused (ANG), high-salt (HS), ANG high-salt (ANG/HS), placebo, and deoxycorticosterone acetate-salt rats were studied. Third-order mesenteric arteries from ANG or ANG/HS displayed decreased sensitivity to acetylcholine (ACh)-induced vasorelaxation compared with NORM or HS, respectively. Maximal relaxations were comparable between groups. Blockade of Ca 2ϩ -activated K ϩ channels had no effect on ANG versus blunting relaxation in NORM (log EC 50 : Ϫ6.8Ϯ0.1 versus Ϫ7.2Ϯ0.1 mol/L). NO synthase (NOS) inhibition abolished ACh-mediated relaxation in small arteries from ANG, ANG/HS, and deoxycorticosterone acetate-salt versus blunting relaxation in NORM, HS, and placebo (% maximal relaxation: ANG: 2.7Ϯ1.8; ANG/HS: 7.2Ϯ3.2; NORM: 91Ϯ3.1; HS: 82.1Ϯ13.3; deoxycorticosterone acetate-salt: 35.2Ϯ17.7; placebo: 79.3Ϯ10.3), indicating that NOS is the primary vasorelaxation pathway in these arteries from hypertensive rats. We hypothesized that NO/cGMP signaling and NOS-dependent H 2 O 2 maintains vasorelaxation in small arteries from ANG. ACh increased NOS-dependent cGMP production, indicating that NO/cGMP signaling is present in small arteries from ANG (55.7Ϯ6.9 versus 30.5Ϯ5.1 pmol/mg), and ACh stimulated NOS-dependent H 2 O 2 production (ACh: 2.8Ϯ0.2 mol/mg; N -nitro-L-arginine methyl ester hydrochlorideϩACh: 1.8Ϯ0.1 mol/mg) in small arteries from ANG. H 2 O 2 induced vasorelaxation and catalase blunted ACh-mediated vasorelaxation. In conclusion, Ca 2ϩ -activated K ϩ channel-mediated relaxation is dysfunctional in small mesenteric arteries from hypertensive rats, and the NOS pathway compensates to maintain vasorelaxation in these arteries through NOS-mediated cGMP and H 2 O 2 production.

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“…9,10 We have previously shown that EDHF-mediated hyperpolarization and relaxation were decreased in the superior mesenteric arteries of 12-month-old spontaneously hypertensive rats (SHR) compared with age-matched normotensive Wistar-Kyoto rats and that the impairment of the EDHF pathway accounted, at least in part, for the endothelial dysfunction in this model. 11 Several mechanisms have been proposed to explain the reduced EDHF-mediated responses in mesenteric arteries of SHR: change in the expression profile of gap junctions, [12][13][14] increased activity of calcium-activated chloride channels 15 and reduced expression of small conductance calciumdependent potassium channels. 16 In contrast, Sofola et al 17 have reported that EDHF-like relaxation is upregulated in the mesenteric arteries of Sprague-Dawley rats fed a high-salt diet to compensate for the loss of NO.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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This study was designed to determine whether a high-salt diet would alter endothelial function and, if so, the relative contributions of endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) to any changes in vasomotor responses. Male Dahl salt-sensitive (DS) rats were given either a high-salt diet (8% NaCl, DS-H) or a low-salt diet (0.4% NaCl, DS-L) for 6 weeks. Membrane potentials and contractile responses were recorded from the isolated superior mesenteric arteries. After salt loading, DS-H developed hypertension, while DS-L remained normotensive. No difference was found in acetylcholine (ACh)-induced, endothelium-dependent relaxation between the groups. However, after treatment with indomethacin and NO synthase inhibitor, EDHF-like relaxation was significantly greater in DS-H than in DS-L. In contrast, NO-mediated relaxation was significantly smaller in DS-Hthan in DS-L. Iberiotoxin (IbTx), a specific blocker of large-conductance calcium-dependent potassium (BKCa) channels, attenuated EDHF-like relaxation in DS-H but not in DS-L. IbTx marginally inhibited EDHFmediated hyperpolarization only in DS-H. Endothelium-independent relaxation in response to sodium nitroprusside or levcromakalim was similar in both groups. In conclusion, EDHF-like relaxation is upregulated through the activation of BKCa channels in the mesenteric arteries of DS-H. As the overall relaxation in response to ACh did not differ between the groups, the upregulation of EDHF appears to compensate for the loss of NO in the mesenteric arteries of DS-H.

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Attenuation of conducted vasodilatation in rat mesenteric arteries during hypertension: role of inwardly rectifying potassium channels

Cited by 82 publications

References 46 publications

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two‐compartment in vitro set‐up

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two‐compartment in vitro set‐up

Novel Nitric Oxide Synthase–Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats

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

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