Nonadrenergic noncholinergic relaxation of human pulmonary arteries is partially mediated by nitric oxide.
Nonadrenergic noncholinergic (NANC) vasodilator mechanisms may contribute to the maintenance of low vascular resistance characteristic of the pulmonary circulation. Previous studies have demonstrated that nitric oxide (NO) is the principal NANC neurotransmitter in guinea pig pulmonary arteries. We examined whether NANC relaxation could be demonstrated in human pulmonary arteries, and the role of NO in this phenomenon. Fresh human pulmonary artery rings, with and without an intact endothelium, were mounted in organ baths containing Krebs' solution and precontracted with U44069 (0.3 microM). Adrenergic and cholinergic neurotransmitter pathways were blocked with guanethidine and atropine, respectively (10 microM each). In both endothelium-intact and -denuded vessels, electrical field stimulation (EFS, 1 to 10 Hz, 100 V) resulted in a frequency-dependent relaxation (maximal relaxation of 25 +/- 4% and 15 +/- 2% in endothelium-intact and -denuded vessels, respectively). Tetrodotoxin (0.3 microM) abolished the EFS-induced relaxation. L-NG-nitro-arginine methyl ester (L-NAME, 10 microM), was used to block enzymatic synthesis of NO. In both endothelium-intact and -denuded vessels, L-NAME reduced NANC relaxation to approximately 50% of control values. This reduction was reversible with the application of L-arginine (100 microM). We conclude that NANC relaxation exists in human pulmonary arteries and that it is partly mediated through NO.
Scott
J A
JA
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
Craig
I
I
McCormack
D G
DG
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*
D004791:Enzyme Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D009569:Nitric Oxide; C028429:U 44069; D001285:Atropine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D006145:Guanethidine