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Impairment of corpus cavernosal smooth muscle relaxation by glycosylated human haemoglobin
Author(s) -
Cartledge J.J.,
Eardley I.,
Morrison J.F.B.
Publication year - 2000
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2000.00599.x
Subject(s) - sodium nitroprusside , endocrinology , medicine , nitric oxide , superoxide dismutase , superoxide , acetylcholine , arginine , catalase , muscle relaxation , pyrogallol , deferoxamine , papaverine , biochemistry , chemistry , oxidative stress , enzyme , amino acid
Objective To examine the effect of HbA 1c , an isoform of glycosylated haemoglobin (GHb, a product of non‐enzymatic reactions between elevated blood glucose and haemoglobin), on nitric oxide‐mediated corpus cavernosal smooth muscle relaxation, and to categorize the mechanisms involved. Materials and methods Corpus cavernosal tissue from Wistar rats (300–350 g body weight) was prepared for the measurement of isometric tension. After equilibration in Krebs solution gassed with 95% O 2 /5% CO 2 at 37 °C for 90 min, optimal resting tension was applied. Tissue was precontracted with 1 µmol/L noradrenaline (NAd) and either relaxed with incremental doses of acetylcholine (ACh) or sodium nitroprusside (SNP). After washout, strips were again precontracted with NAd and then incubated with pyrogallol (100 µmol/L), 100 µL of haemoglobin or 100 µL of GHb in the presence of either l ‐arginine (100 µmol/L), indomethacin (10 µmol/L), allopurinol (100 µmol/L), deferoxamine (100 µmol/L), catalase (600 IU/mL), or superoxide dismutase (SOD) (120 IU/mL) before ACh‐ or SNP‐induced relaxation responses were repeated. Results Haemoglobin and GHb significantly impaired the relaxation of rat corpus cavernosum to ACh in a dose‐dependent manner. l ‐arginine reversed the impairment caused by Hb, but not GHb. A donor of superoxide anions, pyrogallol, mimicked this impairment to ACh when added to control strips. Catalase, deferoxamine, indomethacin and allopurinol had no significant effect on the impaired relaxation response to ACh, whilst l ‐arginine partially reversed it. SOD completely reversed the GHb‐induced impaired relaxation; GHb did not alter the relaxation response to SNP. Conclusion GHb significantly impairs endothelial NO‐mediated corpus cavernosal relaxation in the rat, in vitro. This effect is caused partly by the generation of superoxide anions and the extracellular inactivation of NO.