Regulation of baseline vascular resistance in the canine diaphragm by nitric oxide.
1. The role played by nitric oxide (NO) in the regulation of blood flow to the canine isolated hemidiaphragm was evaluated by determining (a) the effects of the L-arginine analogues NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-L-arginine (L-NOARG), and argininosuccinic acid (ArgSA) on baseline vascular resistance and of the latter two agents on endothelium-dependent (acetylcholine, ACh) and endothelium independent (sodium nitroprusside, SNP) vasodilatation; (b) the effects of L- and D-arginine on baseline vascular resistance; and (c) the effects of L-glutamine, an inhibitor of intracellular recycling of L-citrulline to L-arginine, on baseline resistance and on the response to ACh and SNP. 2. L-NAME, L-NOARG and ArgSA (6 x 10(-4) M final concentration) increased baseline diaphragmatic vascular resistance to a similar extent (28.6 +/- 4.2%, 26.7 +/- 4.3% and 32.8 +/- 4.6% respectively). L-NOARG and ArgSA reversed the vasodilator effect of ACh but not of SNP. 3. L- and D-arginine had no effect on vascular resistance. 4. L-Glutamine (10(-3) M) increased baseline vascular resistance by 10 +/- 1.9% (P < 0.05) but did not alter responses to either ACh or SNP. 5. Basal NO release plays a role in the regulation of baseline diaphragmatic vascular resistance. L-Arginine analogues tested potently and specifically inhibited this process. Moreover, extracellular L-arginine appears to have no effect on baseline diaphragmatic vascular resistance.
Division of Pulmonary and Critical Care Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
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Ward
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Hussain
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001125:Argininosuccinic Acid / Q000494:pharmacology; D003964:Diaphragm / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D066298:In Vitro Techniques; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D019335:Nitroarginine; D001125:Argininosuccinic Acid; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester