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Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesisThe vasodilator effects of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 are subject to tachyphylaxis in rats treated with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). We examined whether this tachyphylaxis could be prevented by administration of the putative endothelium-derived nitrosyl factor S-nitroso-L-cysteine (L-SNC) and whether L-SNC may exert its effects via increases in cGMP levels in vascular smooth muscle. Five doses of PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats. These responses were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME-treated (50 micromol/kg iv) rats produced vasodilator responses similar to those in saline-treated rats, whereas subsequent injections produced progressively smaller responses. The injection of L-SNC (1,200 nmol/kg iv) before each injection of PACAP-27 prevented tachyphylaxis to the Gs protein-coupled receptor agonist in L-NAME-treated rats, whereas equihypotensive doses of the NO donor sodium nitroprusside (100 micrograms/kg iv) did not. The injection of the membrane-permeant cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-CPT-cGMP; 30 micromol/kg iv) to L-NAME-treated rats restored resting hemodynamic values to pre-L-NAME levels but did not prevent the development of tachyphylaxis to PACAP-27. These results suggest that nitrosyl factors prevent the development of tachyphylaxis to the hemodynamic actions of PACAP-27. These nitrosyl factors may act independently of their ability to generate cGMP in vascular smooth muscle.
Document ID
20040141934
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Whalen, E. J.
(University of Iowa Iowa City, Iowa 52242, United States)
Travis, M. D.
Johnson, A. K.
Lewis, S. J.
Date Acquired
August 22, 2013
Publication Date
June 1, 1999
Publication Information
Publication: The American journal of physiology
Volume: 276
Issue: 6 Pt 2
ISSN: 0002-9513
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL-57472
CONTRACT_GRANT: DK-54759
CONTRACT_GRANT: HL-14388
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Regulatory Physiology
Non-NASA Center

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