Endothelium-dependent hyperpolarization: a role in the control of vascular tone

Garland, C J; Plane, Frances; Kemp, B.; Cocks, T. M.

doi:10.1016/s0165-6147(00)88969-5

Cited by 423 publications

(336 citation statements)

References 42 publications

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“…Although NO has generally been considered to be the principal mediator of endothelium-dependent relaxations, it has become increasingly clear that NO-independent endothelium-derived relaxing factors might have an important role in local vasomotor control. Evidence is mounting that EDHF is a major determinant of vascular tone in small resistance vessels [5].…”

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confidence: 99%

The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin - induced diabetic rats is restored by 5-methyltetrahydrofolate

et al. 2000

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Dysfunction of the endothelium is an early and key event in the development of microvascular and macrovascular complications [1], which account for most of the morbidity and mortality of diabetes. Endothelial integrity is generally assessed by evaluating the vasodilator response of a blood vessel or a vascular bed to an endothelium-dependent agonist [2]. Endothelial cells relax the tone of the underlying vascular smooth muscle cells by releasing a number of vasodi- Diabetologia (2000) Abstract Aims/hypothesis. Endothelial dysfunction contributes to the development of diabetic vascular complications. A better understanding of the pathophysiology of endothelial dysfunction in diabetes could lead to new approaches to prevent microvascular disease. Methods. Endothelium-dependent and endotheliumindependent vasodilator responses were investigated in the renal microcirculation of streptozotocin-induced diabetic rats. We measured renal blood flow changes with an electromagnetic flow probe. In addition, the responses of the different segments of the renal microcirculation were evaluated with videomicroscopy using the hydronephrotic kidney technique. Because endothelial cells release different relaxing factors (nitric oxide, prostacyclin and an unidentified endothelium-derived hyperpolarizing factor), responses to acetylcholine were measured before and after treatment with the nitric oxide synthase inhibitor l-N G -nitroarginine methylester HCI (l-NAME) and the cyclooxygenase inhibitor indomethacin. We evaluated with the effect of 5-methyltetrahydrofolate, the active form of folate, on the responses. Results. The l-NAME-and indomethacin-resistant vasodilation to intra-renal acetylcholine was significantly reduced in the diabetic compared with control rats, suggesting impaired endothelium-derived hyperpolarizing factor-mediated vasodilation. The responses to the nitric oxide donor (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate) and to the K + -channel opener pinacidil were similar in diabetics and controls, indicating intact endothelium-independent vasodilator mechanisms. The contribution of endothelium-derived hyperpolarizing factor to vasodilation induced by acetylcholine was greatest in the smallest arterioles. In diabetic rats, the response to acetylcholine was increasingly impared as vessel size decreased. Defective vasodilation in diabetic kidneys was rapidly normalized by 5-methyltetrahydrofolate. Conclusion-interpretation. Endothelium-derived hyperpolarizing factor-mediated vasodilation is impaired in the renal microcirculation of diabetic rats, in particular in the smallest arteries. Treatment with folate restores the impaired endothelial function in diabetes. [Diabetologia (2000

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confidence: 99%

The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin - induced diabetic rats is restored by 5-methyltetrahydrofolate

et al. 2000

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“…Introduction Endothelium-dependent relaxations of blood vessels to agonists such as acetylcholine (ACh) are mediated by nitric oxide (NO), prostanoids and an endothelium-derived hyperpolarizing factor (EDHF) (Taylor & Weston, 1988;Garland et al, 1995). The relative contribution of these factors may vary under di erent experimental conditions as all three may cause hyperpolarization of vascular smooth muscle (Parkington et al, 1993), release of EDHF is attenuated by NO (Bauersachs et al, 1996), and NO may stimulate the synthesis of prostanoids (Salvemini et al, 1993).…”

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confidence: 99%

Inhibition of the gap junctional component of endothelium‐dependent relaxations in rabbit iliac artery by 18‐α glycyrrhetinic acid

Taylor

Chaytor

Evans

et al. 1998

British J Pharmacology

140

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The gap junction inhibitor 18-a-glycyrrhetinic acid (a-GA, 100 mM) attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic acid by *20% in rings of pre-constricted rabbit iliac artery. The nitric oxide synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME, 300 mM) inhibited relaxations to both agents by *65% and these were further attenuated by a-GA to 510% of control. In endothelium-denuded preparations, relaxations to sodium nitroprusside were not a ected by a-GA. Heterocellular gap junctional communication may therefore account for nitric oxide-independent relaxations evoked both by receptor-dependent and -independent mechanisms in rabbit iliac artery.

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“…Coronary vascular tone is regulated by endothelial cells releasing multiple vasoactive compounds that act on smooth muscle cells,17 including nitric oxide, prostacyclin , substance P, and cytochrome P450 monooxygenase (CYP450) metabolites of arachidonic acid. These autacoids are responsible for vasorelaxation of the endothelium in the vasculature 17, 18.…”

Section: Contributing Pathologies Within the Cvd Spectrummentioning

confidence: 99%

“…These autacoids are responsible for vasorelaxation of the endothelium in the vasculature 17, 18. Early atherosclerosis is marked by endothelial dysfunction caused by biochemical and physical injuries, as well as immune‐mediated damages and oxidative stress; resulting in altered platelet and leukocyte adhesion to the vascular surface, initiating an inflammatory response in the artery wall 9, 19.…”

Section: Contributing Pathologies Within the Cvd Spectrummentioning

confidence: 99%