Nonadrenergic noncholinergic vasodilation of guinea pig pulmonary arteries is mediated by nitric oxide.
Nonadrenergic noncholinergic (NANC) mediated vasodilation may contribute to the maintenance of low pulmonary vascular tone. The NANC neurotransmitters, nitric oxide (NO) and the sensory neuropeptides, substance P and calcitonin gene related peptide (CGRP), were investigated as possible mediators of NANC vasodilation in guinea pig pulmonary arteries. Fresh guinea pig pulmonary artery rings, with and without an intact endothelium, were mounted in organ baths containing Krebs solution and precontracted with the prostaglandin F2alpha analogue U44069. In both endothelium-intact and denuded vessels, electrical field stimulation (1-12 Hz) in the presence of guanethidine and atropine resulted in a frequency-dependent vasodilation. The peptide fragment hCGRP8-37, a competitive antagonist of the CGRP receptors, the peptide fragment NK1 antagonist SP4-11, and the nonpeptide NK1 antagonist RP67580 had no effect on NANC vasodilation. In both endothelium-intact and denuded vessels, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, inhibited NANC vasodilation, an effect that was reversible with L-arginine. We conclude that NANC vasodilation in guinea pig pulmonary arteries is mediated predominantly through NO activity.
Scott
J A
JA
Department of Pharmacology and Toxicology, Faculty of Medicine, The University of Western Ontario, and London Health Sciences Centre, Canada.
McCormack
D G
DG
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000294:innervation / Q000502:physiology*; D013373:Substance P / Q000502:physiology; D014664:Vasodilation
D007211:Indoles; D054833:Isoindoles; D011450:Prostaglandin Endoperoxides, Synthetic; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D009569:Nitric Oxide; D013373:Substance P; C028429:U 44069; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester