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Impaired vasomotor function in uremic rats is directly related to NO‐resistance of smooth muscle cells
Author(s) -
Kolk Felix,
Molin D.G.M,
De Mey J.G.R,
Post M.J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.866.12
Subject(s) - myograph , medicine , vasomotor , vasodilation , endocrinology , endothelial dysfunction , nitric oxide , uremia , acetylcholine
The number of patients with renal failure is 240 million worldwide, with 20% being dependent on dialysis. Renal failure increases the risk to develop cardiovascular diseases and could be related to vessel wall dysfunction. Gaining a better understanding of arterial dysfunction under uremic conditions and especially its effect on NO‐soluble guanylate cyclase (sGC) mediated vasorelaxation. For uremic rats, 5/6 nephrectomy (n=21) was performed in Wistar rats. After six weeks, both carotid arteries were removed and analyzed in a wire‐myograph. Different compounds were used to investigate NO‐dependent and ‐independent vasomotor pathways. SNP and Deta NONOate showed significant differences in vasorelaxation between sham and 5/6 nephrectomy group with a 0.5 log IC50 difference in NO‐induced relaxation (P<0.0001). This difference was endothelial independent as acetylcholine induced effects were blocked with L‐NAME. Also NO independent, but sGC heam dependent and independent, (Bay 41‐2272 and Bay 60‐2770, respectively) vasorelaxation showed significant differences (p<0.01 and p<0.0001). When sGC was oxidized with ODQ, sham group was more potent in relaxation for both compounds as compared to uremic rats. Reduced vasorelaxation in uremic rats is related to NO‐resistance of smooth muscle cells. Our results point toward an oxidized state of sGC as the main cause of vasomotor dysfunction in uremic rats.