Correlation with blood pressure of the acetylcholine-induced endothelium-derived contracting factor in the rat aorta.

Iwama, Yoshio; Kato, Teiji; Muramatsu, Masaaki; Asano, Hiroshi; Shimizu, Keiko; Toki, Yukio; Miyazaki, Yoshiji; Okumura, Kenji; Hashimoto, Hiroyuki; Itō, Takayuki

doi:10.1161/01.hyp.19.4.326

Cited by 68 publications

(45 citation statements)

References 29 publications

(20 reference statements)

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“…The effects of the isoflavones, 17␤-estradiol, or vehicle were also studied on the contractions evoked by the TP receptor agonist U46619 in endothelium-denuded vessels. In preliminary experiments, both the relaxant and contractile responses to acetylcholine were fully abolished by mechanical removal of endothelium as reported previously (Iwama et al, 1992).…”

Section: Methodssupporting

confidence: 74%

Soy Isoflavones Improve Endothelial Function in Spontaneously Hypertensive Rats in an Estrogen-Independent Manner: Role of Nitric-Oxide Synthase, Superoxide, and Cyclooxygenase Metabolites

Vera¹,

Galisteo²,

Villar³

et al. 2005

J Pharmacol Exp Ther

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The aim of this study was to analyze the effects of the isoflavones genistein and daidzein, and the mammalian estrogen 17␤-estradiol on endothelial function in isolated aortic rings from male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Relaxation to acetylcholine on precontracted rings was impaired and endothelium-dependent contraction to acetylcholine in aortic rings was increased in SHR compared with WKY. Aortic NADPH-stimulated O 2 Ϫ release and prostaglandin (PG)H 2 production evoked by acetylcholine were increased, whereas nitric-oxide synthase activity was reduced in SHR versus WKY. Genistein, daidzein, or 17␤-estradiol enhanced the relaxant response to acetylcholine and decreased the endothelium-dependent vasoconstrictor responses to acetylcholine in SHR, but not in WKY, and these effects were not modified by the estrogen receptor antagonist ICI 182,780 (7␣,4,5,5,5-pentafluoropentyl)-sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol). Moreover, isoflavones enhanced nitric-oxide (NO) synthase activity and inhibited NADPH-stimulated O 2 Ϫ roduction and endothelial release of PGH 2 . The contractions induced by the TP receptor agonist U46619 (9,11-dideoxy-11␣,9␣-epoxymethanoprostaglandin F 2␣ ) in denuded aortic rings were inhibited by genistein, daidzein, and 17␤-estradiol in both strains. In conclusion, the isoflavones genistein and daidzein and 17␤-estradiol restore endothelial function in male SHR through estrogen receptor-independent mechanisms. Increased NO production and protection of NO from O 2 Ϫ -driven inactivation might be involved in the improvement of vascular relaxation to acetylcholine in aortic rings from SHR. Moreover, isoflavones and 17␤-estradiol inhibited aortic endothelium-dependent contraction to acetylcholine in SHR by reducing the endothelial PGH 2 release and its vasoconstrictor response.

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Section: Methodssupporting

confidence: 74%

Soy Isoflavones Improve Endothelial Function in Spontaneously Hypertensive Rats in an Estrogen-Independent Manner: Role of Nitric-Oxide Synthase, Superoxide, and Cyclooxygenase Metabolites

Vera¹,

Galisteo²,

Villar³

et al. 2005

J Pharmacol Exp Ther

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“…3 * Furthermore, a correlation between the expression of endothelium-dependent contractions and increase in arterial blood pressure has been reported in SHR. 39 These findings strongly support the concept that the production of superoxide anions mediated by cyclooxygenase activation may play a role in the development of high arterial tone in hypertension. Indeed, as in SHR, 2 treatment of hypertensive patients with indomethacin improves endothelium-dependent relaxations to acetylcholine.…”

supporting

confidence: 73%

Role of superoxide anions in the mediation of endothelium-dependent contractions.

1994

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We designed experiments to characterize the role of superoxide anions in the mediation of endothelium-dependent contractions in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% Oj-6% CO 2 (37°C, pH 7.4). Radioimmunoassay was used to determine the levels of cyclic GMP and cyclic AMP. Calcium ionophore A23187 (1(T 9 to 1(T 6 mol/L) caused concentration-dependent contractions. The removal of endothelium abolished the effect of A23187. Contractions to A23187 were reversed into relaxations in the presence of superoxide dismutase (150 U/mL) or the prostaglandin H 2 /thromboxane A 2 receptor antagonist SQ29548 (10~6 mol/L). Af G -nitro-Larginine methyl ester (3xlO~4 mol/L) augmented contractions to A23187. In rings with endothelium, A23187 (3 x 1(T 7 mol/L) significantly increased levels of both cyclic AMP and cyclic GMP. Indomethacin (10~5 mol/L) inhibited stimulatory effects of A23187 on cyclic AMP production. In contrast, indomethacin augmented A23187-induced production of cyclic GMP. Selective augmentation of cyclic GMP production by indomethacin appears to be due to protection of nitric oxide or a closely related molecule released following translocation of calcium into endothelial cells. Our findings suggest that (1) an increased concentration of calcium in endothelial cells may activate both cyclooxygenase and the L-arginine/nitric oxide pathway, (2) arachidonic acid metabolism via cyclooxygenase is a source of superoxide anions, and (3) superoxide anions may be responsible for impairment of balance between relaxing and contracting factors leading to contraction of underlying smooth muscle cells. (Hypertension. 1994^3:229-235.)

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“…99 Endotheliumdependent contractions become more prominent in arteries of older compared with younger animals. 21,101,102 This increased response is accompanied by an increased expression of COX-1. 46 When COX-2 is induced by the aging process or by disease, this isoform of the enzyme can contribute in part to endothelium-dependent contractions.…”

Section: Hallmark Of Vascular Diseasementioning

confidence: 99%

Endothelium-Dependent Contractions in Hypertension

2011

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M ost isolated arteries respond to shear stress and several vasodilator substances, as demonstrated first for acetylcholine, 1 by releasing endothelium-derived relaxing factor (or nitric oxide [NO]), and various endothelium-derived hyperpolarizing signals. [2][3][4][5] However, in certain blood vessels, when exposed to stretch, agonists such as thrombin, acetylcholine, and adenosine nucleotides (adenosine diphosphate [ADP] and adenosine triphosphate [ATP]) or calcium ionophores, the endothelium produces diffusible cyclooxygenase (COX)-derived vasoconstrictor prostanoids (endotheliumderived contracting factors [EDCF]) 6 -11 Endothelial cells also produce vasoconstrictor peptides, in particular, endothelin-1. 12 The attribution of a role to endothelin-1 in instantaneous changes in vascular tone has been made difficult by the almost insurmountable nature of the vasoconstriction caused by the peptide that can only be tempered by NO or calcitonin gene-related peptide. 13,14 Likewise, the evidence linking acute release of endothelin-1 to constriction of arteries is still limited. 15 Therefore, the present article focuses on the mechanisms leading to the production of endothelial COX-derived vasoconstrictors, in particular, in the rat aorta, which has been the standard preparation used by the author and his collaborators for the study of EDCF-mediated responses However, the occurrence of such EDCF-mediated responses can vary widely, depending on the species and the blood vessel studied. For example, they are prominent in canine veins but not arteries. 6 In the mouse, endothelium-dependent contractions are more pronounced in the carotid artery than in the aorta. 16,17 Further, in any given blood vessel, the production of endothelium-derived vasoconstrictor prostanoids is exacerbated by aging and disease, in particular, hypertension. 10,11,18,19 The Trigger: Calcium Acetylcholine (which activates endothelial M3-muscarinic receptors) 20 and ADP and ATP (which activate endothelial purinoceptors) 21,22 evoke endothelium-dependent contractions and release of calcium from the sarcoplasmic reticulum. 23 Lowering the extracellular calcium concentration reduces endothelium-dependent contractions, 24 whereas calcium ionophores, in particular, A23187, evoke endotheliumdependent contractions. [25][26][27][28][29] During endothelium-dependent contractions induced by acetylcholine, the endothelial cytosolic calcim concentration increases 28,29 and this increment is larger in aortae of spontaneously hypertensive rats (SHR) than in those of normotensive Wistar-Kyoto rats, in line with the larger EDCF-mediated responses in the preparations of the hypertensive strain. 8,28,30 Taken in conjunction, those findings imply that an increase in endothelial cytosolic calcium concentration is the initiating event leading to the release of EDCF. In the case of acetylcholine, the muscarinic agonist binds to G-protein-coupled M 3 receptors on the endothelial cell membrane and activates phospholipase C, which produces inositol triphosphate, causing...

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Correlation with blood pressure of the acetylcholine-induced endothelium-derived contracting factor in the rat aorta.

Cited by 68 publications

References 29 publications

Soy Isoflavones Improve Endothelial Function in Spontaneously Hypertensive Rats in an Estrogen-Independent Manner: Role of Nitric-Oxide Synthase, Superoxide, and Cyclooxygenase Metabolites

Soy Isoflavones Improve Endothelial Function in Spontaneously Hypertensive Rats in an Estrogen-Independent Manner: Role of Nitric-Oxide Synthase, Superoxide, and Cyclooxygenase Metabolites

Role of superoxide anions in the mediation of endothelium-dependent contractions.

Endothelium-Dependent Contractions in Hypertension

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