Guanylate Cyclase Activators Influence Reactivity of Human Mesenteric Superior Arteries Retrieved and Preserved in the Same Conditions as Transplanted Kidneys

• Published in: Transplantation proceedings Vol. 39; no. 5; pp. 1350 - 1353
• Main Authors: Slupski, M, Szadujkis-Szadurski, L, Grześk, G, Szadujkis-Szadurski, R, Szadujkis-Szadurska, K, Wlodarczyk, Z, Masztalerz, M, Piotrowiak, I, Jasiński, M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2007; Elsevier Science
• Subjects: Biological and medical sciences; Blood Pressure - drug effects; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors - therapeutic use; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Indazoles - therapeutic use; Kidney Transplantation - physiology; Medical sciences; Mesenteric Artery, Superior - drug effects; Mesenteric Artery, Superior - physiology; NG-Nitroarginine Methyl Ester - therapeutic use; Organ Preservation; Oxadiazoles - therapeutic use; Platelet Aggregation Inhibitors - therapeutic use; Quinoxalines - therapeutic use; Retrospective Studies; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - therapeutic use; Human; Graft(material); Enzyme; Phosphorus-oxygen lyases; Lyases; Transplantation; Guanylate cyclase; Homotransplantation; Kidney; Medicine; Reactivity; Treatment; Urinary system; Activator; Superior mesenteric artery; Surgery; Graft
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2007.02.079

Abstract Introduction This study sought to investigate the mechanisms of relaxation induced by the (nitric oxide (NO)-independent soluble guanylyl cyclase (sGC) stimulators 3-[5′-hydroxymethyl-2′-furyl]-1-benzylindazole (YC-1) in human mesenteric arteries relaxed and precontracted with 1 μmol/L 5-hydroxytryptamine (serotonin). Material and methods Human mesenteric arteries obtained during kidney retrieval were preserved in the same conditions as transplanted kidneys. All experiments were performed after reperfusion with Krebs buffer in 37°C and 100% oxygen exposure. Results In endothelium-intact rings, YC-1 (0.001 to 30 mmol/L) caused concentration-dependent relaxation (pEC50 : 6.59 ± 0.12), which shifted to the right in endothelium-denuded rings. The sGC inhibitor 1 H - [1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ 10 mmol/L) partially attenuated the maximal responses to YC-1 (Emax = 51.30% ± 3.70%; n = 6) and displaced its curve to the right in intact and denuded vessels. Both, the NO synthesis inhibitor N-nitro-L-arginine methyl ester (100 mmol/L) and the NO scavenger carboxy-2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (100 mmol/L) significantly reduced YC-1 relaxation. The sodium pump inhibitor ouabain (1μmol/L) produced a greater decrease in the vasodilator response of YC-1 (Emax = 18.7% ± 4.55%; n = 9). ODQ (10 μmol/L) plus 1 μmol/L ouabain abolished the relaxant response of YC-1 (Emax = 9.4% ± 2.94%, n = 9). Conclusions This study demonstrated that sodium pump stimulation by YC-1 as an additional mechanism of sGC activation independent of cGMP relaxed human mesenteric artery, including blockade of Ca2+ influx. Furthermore, this study suggested an ability of NO to mediate relaxation of resistance-like arteries through the activation of soluble guanylate cyclase and K+ channels.