Hoenicka, Markus and Keyser, Andreas and Rupprecht, Leopold and Puehler, Thomas and Hirt, Stephan and Schmid, Christof (2011) Endothelium-Dependent Vasoconstriction in Isolated Vessel Grafts: A Novel Mechanism of Vasospasm? ANNALS OF THORACIC SURGERY, 92 (4). pp. 1299-1306. ISSN 0003-4975, 1552-6259
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Background. YC-1 (3-(5'-hydroxymethyl-2'furyl)-1-benzyl- indazole) is an allosteric activator of soluble guanylyl cyclase (sGC) and a vasodilator. This study describes a paradoxical action of YC-1 in isolated vessels of patients with coronary artery disease (CAD) that appears to trigger an endothelium-dependent vasoconstrictor pathway present in vessels with endothelial dysfunction. Methods. Effects of YC-1 on the tensions of isolated vessels were investigated in an organ bath. Vasoconstrictors released from the vessels were quantified through enzyme-linked immunosorbent assay. Results. YC-1 elicited long-lasting constriction in saphenous veins and radial arteries from patients with CAD, but not in human umbilical veins. The half-maximal effective dose was 1.0 mu mol/L. Constriction was attenuated by nifedipine (an L-type Ca2+-channel blocker), bosentan (an endothelin [ET](A)/ETB inhibitor), BQ-788 (N-[(cis-2,6-Dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-leucyl-1-(methoxycarbonyl)-D-tryptophyl-D-norleucine; an ETB inhibitor), and by denuding, but not by ODQ (1H-(1,2,4) oxadiazolo[4,3-a]quinoxalin-1-one; an inhibitor of sGC), BQ-123 (cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu); an ETA inhibitor), or phosphoramidon (an endothelin converting enzyme inhibitor). Indomethacin (an inhibitor of cyclooxygenase-1 and -2) and SQ29,548 ([1S-[1 alpha,2 alpha (Z), 3 alpha,4 alpha]]-7-[3-[[2-[(phenylamino) carbonyl] hydrazino] methyl]-7-oxabicyclo[2.2.1] hept-2-yl]-5-heptenoic acid; a thromboxane receptor antagonist) suppressed YC-1-induced constriction, whereas DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone; a cyclooxygenase-2 inhibitor) had no effect. Rings of saphenous vein released significantly more endothelin-1 in the presence than in the absence of YC-1. Conclusions. YC-1-induced vasoconstriction demonstrates the existence of an endothelium-dependent vasoconstrictor pathway in the blood vessels of patients with CAD that to date has been described only in animal models of hypertension. Patients with CAD who have elevated plasma levels of endothelin-1 are thus prone to endothelium-dependent vasoconstriction, which may also play a role in vasospasm in vascular grafts. (Ann Thorac Surg 2011;92:1299-307) (C) 2011 by The Society of Thoracic Surgeons
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SOLUBLE GUANYLYL CYCLASE; NITRIC-OXIDE; SMOOTH-MUSCLE; CONTRACTING FACTORS; CARBON-MONOXIDE; SODIUM-PUMP; RAT AORTA; IN-VIVO; YC-1; CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 May 2020 08:55 |
| Last Modified: | 28 May 2020 08:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20034 |
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