Insulin Stimulates Both Endothelin and Nitric Oxide Activity in the Human Forearm
Carmine Cardillo,Sridhar S. Nambi,Crescence M. Kilcoyne,Wassim K Choucair,Arie Katz,Michael J. Quon,Julio A. Panza +6 more
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TL;DR: Findings suggest that in the skeletal muscle circulation, insulin stimulates both ET-1 and NO activity, an imbalance between the release of these 2 substances may be involved in the pathophysiology of hypertension and atherosclerosis in insulin-resistant states associated with endothelial dysfunction.
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Abstract: Background—The mechanism of the hemodynamic effect of insulin in the skeletal muscle circulation has not been fully elucidated. The purpose of this study was to assess whether the hemodynamic response to insulin involves the concurrent release of endothelin (ET-1) and nitric oxide (NO), 2 substances with opposing vasoactive properties. Methods and Results—Bioactivity of ET-1 and NO was assessed without insulin and during insulin infusion in the forearm circulation of healthy subjects by use of blockers of ET-1 receptors and by NO synthesis inhibition. In the absence of hyperinsulinemia, ET-1 receptor blockade did not result in any significant change in forearm blood flow from baseline (P=0.29). Intra-arterial insulin administration did not significantly modify forearm blood flow (P=0.88). However, in the presence of hyperinsulinemia, ET-1 receptor antagonism was associated with a significant vasodilator response (P<0.001). In the presence of ET-1 receptor blockade, the vasoconstrictor response to NO inhib...
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References
Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor.
Masaki Ihara,Kazuhito Noguchi,Toshihiko Saeki,Takahiro Fukuroda,Sonoko Tsuchida,Sachiyo Kimura,Takehiro Fukami,Kiyofumi Ishikawa,Masaru Nishikibe,Mitsuo Yano +9 more
TL;DR: Novel potent endothelin (ET) antagonists that are highly potent and selective for the ETA receptor (selective to ET-1) are described, which should provide a powerful tool for exploring the therapeutic uses of ETA antagonists in putativeET-1-related disorders.
918
Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells.
Gang Zeng,Michael J. Quon +1 more
TL;DR: The data suggest that NO is a novel effector of insulin signaling pathways that are also involved with glucose metabolism, and that PI 3-kinase activity is required for insulin-stimulated glucose transport.
Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension.
TL;DR: It is indicated that patients with essential hypertension have a defect in the endothelium-derived nitric oxide system that may at least partly account for both the increased vascular resistance under basal conditions and the impaired response to endothelia-dependent vasodilators.
750
Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788
K. Ishikawa,Masaki Ihara,K. Noguchi,T. Mase,N. Mino,T Saeki,Takahiro Fukuroda,Takehiro Fukami,S. Ozaki,Takahiro Nagase +9 more
TL;DR: Being a potent and selective ETB receptor antagonist, BQ-788 may be considered as a powerful tool for investigating the role of ET in physiological and pathological processes.
591
Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels.
TL;DR: Vascular smooth muscle cells of human IMA, IMV, and PCA contain both ETA and ETB receptors, whereas the endothelium of IMA andPCA does not express functional ETB receptor linked to nitric oxide and/or prostacyclin production, and inhibition of endothelin-induced contraction in patients requires the use of combined ETA/ETB antagonists.
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