The effect of arginine and nitric oxide on resistance blood vessels of the perfused rat kidney.
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 mumol) caused a biphasic change in renal perfusion pressure. D-Arginine (0.6-23 mumol) 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 ED50 of 2.2 +/- 0.4 mumol (n = 6). The rank order of potency of the salts tested was: methylester greater than hydroxamate greater than chloride. L-Homoarginine chloride was also vasodilator (ED50, 12.0 +/- 1.3 mumol, n = 5). D-Arginine chloride was without effect at doses up to 170 mumol. Responses to L-arginine chloride were endothelium-derived relaxing factor (EDRF)-dependent being abolished by CHAPS (4.7 mg ml-1, 30 s) and significantly inhibited (greater than 70%) by gossypol (3 microM) and nordihydroguaiaretic acid (NDGA, 10 microM). 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 microM) or L-canavanine (50 microM) showed no change in sensitivity towards ACh or NP. Higher concentrations of L-arginine chloride (500 microM) or L-canavanine (150 microM) 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..
Biomedical Sciences Division, King's College, University of London.
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Bhardwaj
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Moore
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects; D002172:Canavanine / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D009599:Nitroprusside; D009569:Nitric Oxide; D002172:Canavanine; D001120:Arginine; D000109:Acetylcholine