Premium
Acetylcholine‐induced vasodilation may depend entirely upon NO in the femoral artery of young piglets
Author(s) -
Støen Ragnhild,
Lossius Kristin,
Karlsson Jan Olof G
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705001
Subject(s) - apamin , charybdotoxin , sodium nitroprusside , acetylcholine , chemistry , ouabain , vasodilation , pharmacology , medicine , potassium channel , potassium channel blocker , endocrinology , phenylephrine , nitric oxide , anesthesia , sodium , organic chemistry , blood pressure
To characterize agonist‐induced relaxation in femoral artery rings from young piglets, we compared the effect of a NOS‐inhibitor N ω ‐nitro‐ L ‐arginine ( L ‐NOARG), an NO‐inactivator oxyhaemoglobin (HbO) and a soluble guanyl cyclase(sGC)‐inhibitor 1 H ‐[1,2,4]Oxadiazolo‐[4,3,‐α]quinoxalin‐1‐one (ODQ) on acetylcholine(ACh)‐induced relaxation. The involvement of K + channel activation was studied on relaxations induced by ACh, the two NO donors sodium nitroprusside (SNP) and diethylamine (DEA) NONOate, and the cell membrane permeable guanosine 3′5′ cyclic monophosphate (cGMP) analogue 8‐Br‐cGMP. Full reversal of phenylephrine‐mediated precontraction was induced by ACh (1 n M –1 μ M ) (pD 2 8.2±0.01 and R max 98.7±0.3%). L ‐NOARG (100 μ M ) partly inhibited relaxation (pD 2 7.4±0.02 and R max 49.6±0.8%). The L ‐NOARG/indomethacin(IM)‐resistant response displayed characteristics typical for endothelium‐derived hyperpolarizing factor (EDHF), being sensitive to a combination of the K + channel blockers charybdotoxin (CTX) (0.1 μ M ) and apamin (0.3 μ M ). ODQ (10 μ M ) abolished relaxations induced by ACh and SNP. L ‐NOARG/IM‐resistant relaxations to ACh were abolished by HbO (20 μ M ). Ouabain (1 μ M ) significantly inhibited ACh‐induced L ‐NOARG/IM‐resistant relaxations and relaxations induced by SNP (10 μ M ) and 8‐Br‐cGMP (0.1 m M ). A combination of ouabain and Ba 2+ (30 μ M ) almost abolished L ‐NOARG/IM‐resistant ACh‐induced relaxation (R max 7.7±2.5% vs 23.4±6.4%, with and without Ba 2+ , respectively, P <0.05). The present study demonstrates that in femoral artery rings from young piglets, despite an L ‐NOARG/IM‐resistant component sensitive to K + channel blockade with CTX and apamin, ACh‐induced relaxation is abolished by sGC‐inhibition or a combination of L ‐NOARG and HbO. These findings suggest that relaxation can be fully explained by the NO/cGMP pathway.British Journal of Pharmacology (2003) 138 , 39–46. doi: 10.1038/sj.bjp.0705001