Document Detail

Nitric oxide inhibition unmasks ischemic myocardium-derived vasoconstrictor signals activating endothelin type A receptor of coronary microvessels.
MedLine Citation:
PMID:  15749745     Owner:  NLM     Status:  MEDLINE    
NO plays an important role in the compensatory increase in coronary flow conductance against myocardial ischemia, and NO bioavailability is impaired in various diseases. We tested the hypothesis that, when NO production is inhibited, vasoconstrictor signals from the ischemic myocardium are unmasked. We investigated the involvement of endothelin type A (ETA) receptors in the transduction of the constrictor signal. To detect coronary vasoactive signals derived from ischemic myocardium, we used a bioassay system in which an isolated rabbit coronary microvessel (detector vessel, DV) was placed on beating myocardium perfused by the left anterior descending coronary artery (LAD) of an anesthetized open-chest dog (n = 38). The DV was pressurized to 60 cmH2O throughout the experiment and observed with an intravital microscope equipped with a floating objective. After the intrinsic tone of the DV was established, vehicle (n = 7), Nomega-nitro-L-arginine (L-NNA, 100 micromol/l; n = 13), L-NNA + BQ-123 (a selective ETA receptor blocker, 1 micromol/l; n = 7), or BQ-123 alone (1 micromol/l; n = 7) was superfused onto the DV. Thereafter, the LAD of the beating heart was occluded. Coronary occlusion produced significant dilation of the DV by 10 +/- 4%. When L-NNA was applied, the DV significantly constricted by 12 +/- 5% in response to LAD occlusion, and BQ-123 abolished the vasoconstriction. Pretreatment with BQ-123 alone produced an enhancement of the ischemia-induced dilation. We conclude that ischemic myocardium releases transferable vasomotor signals that produce coronary microvascular constriction during the blockade of NO production and the constrictor signal is mediated by ETA receptors.
Katsuaki Takahashi; Tatsuya Komaru; Satoru Takeda; Kouichi Sato; Hiroshi Kanatsuka; Kunio Shirato
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-03-04
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  289     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-17     Completed Date:  2005-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H85-91     Citation Subset:  IM    
Dept. of Cardiovascular Medicine, Tohoku Univ. Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan.
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MeSH Terms
Coronary Vessels / drug effects,  metabolism*
Endothelin-1 / blood
Enzyme Inhibitors / pharmacology
Myocardial Ischemia / physiopathology*
Nitric Oxide / antagonists & inhibitors*
Nitroarginine / pharmacology
Peptides, Cyclic / pharmacology
Receptor, Endothelin A / antagonists & inhibitors,  metabolism*
Receptors, Endothelin / antagonists & inhibitors
Signal Transduction*
Reg. No./Substance:
0/Endothelin-1; 0/Enzyme Inhibitors; 0/Peptides, Cyclic; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 10102-43-9/Nitric Oxide; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 2149-70-4/Nitroarginine

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