Endothelium-dependent vasoconstriction in isolated vessel grafts: a novel mechanism of vasospasm?

URN to cite this document:: urn:nbn:de:bvb:355-epub-224330
DOI to cite this document:: 10.5283/epub.22433

Hoenicka, Markus

; Keyser, Andreas ; Rupprecht, Leopold ; Puehler, Thomas ; Hirt, Stephan ; Schmid, Christof

Preview

PDF
(1MB)

Date of publication of this fulltext: 24 Oct 2011 11:41

Alternative links to fulltext:Pubmed DOI

Details

Preview

Indexed in

Export bibliographical data

Abstract

Abstract

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

Owner only: item control page

Download Statistics

Altmetric

Alternative Statistics (altmetrics)

More literature (via CORE)

Details

Preview

Indexed in

Export bibliographical data

Abstract

Abstract

Download Statistics

Downloads

Alternative Statistics (altmetrics)

More literature (via CORE)

University Library