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The effect of arginine and nitric oxide on resistance blood vessels of the perfused rat kidney
Author(s) -
Bhardwaj R.,
Moore P.K.
Publication year - 1989
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 - 10.1111/j.1476-5381.1989.tb12011.x
Subject(s) - nitric oxide , arginine , vasodilation , chemistry , sodium nitroprusside , endocrinology , endothelium , medicine , endothelium derived relaxing factor , nordihydroguaiaretic acid , acetylcholine , pharmacology , biochemistry , amino acid , enzyme , arachidonic acid
1 The vasodilator effects of arginine, nitric oxide (NO), acetylcholine (ACh) and sodium nitroprusside (NP) in the noradrenaline‐preconstricted (‘high tone’) perfused rat kidney have been examined. 2 L‐Arginine (0.6–23 μmol) caused a biphasic change in renal perfusion pressure. D‐Arginine (0.6–23 μmol) was without effect. The second vasodilator component was abolished and the first vasoconstrictor effect augmented following CHAPS‐induced removal of the vascular endothelium suggesting that vasodilatation was endothelium‐dependent. 3 L‐Arginine salts produced transient and dose‐related vasodilatation. L‐Arginine methylester was the most potent with an ED 50 of 2.2 ± 0.4 μmol ( n = 6). The rank order of potency of the salts tested was: methylester > hydroxamate > chloride. L‐Homoarginine chloride was also vasodilator (ED 50 , 12.0 ± 1.3 μmol, n = 5). D‐Arginine chloride was without effect at doses up to 170 μmol. Responses to L‐arginine chloride were endothelium‐derived relaxing factor (EDRF)‐dependent being abolished by CHAPS (4.7 mg ml −1 , 30s) and significantly inhibited (>70%) by gossypol (3 μ m ) and nordihydroguaiaretic acid (NDGA, 10 μ m ). 4 Vasodilatation due to NO was unaffected by CHAPS and gossypol treatment but inhibited by NDGA. NO was approximately 3 times less potent than ACh but 3000 times more potent than L‐arginine methylester. 5 Kidneys perfused for 1 h with Krebs solution containing L‐arginine chloride (100 μ m ) or L‐canavanine (50 μ m ) showed no change in sensitivity towards ACh or NP. Higher concentrations of L‐arginine chloride (500 μ m ) or L‐canavanine (150 μ m ) significantly reduced the response to both vasodilators. 6 L‐Arginine salts dilate resistance blood vessels of the perfused rat kidney by a mechanism which may involve the release of EDRF from vascular endothelial cells of the perfused rat kidney.