Document Detail


Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo.
MedLine Citation:
PMID:  3677343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension (200 mm Hg for 10 seconds to 15 minutes). In open-chest anesthetized dogs, the left anterior descending coronary artery was perfused at constant pressure. Coronary diameter (D) was measured with piezoelectric crystals. At a control perfusion pressure of 80 mm Hg, serotonin produced dose-dependent constriction of the large coronary artery (mean +/- SEM; delta D = -22 +/- 10 microns at 5 micrograms/min; -108 +/- 50 microns at 50 micrograms/min). Increasing perfusion pressure to 200 mm Hg increased flow 515 +/- 79% and coronary diameter 509 +/- 9 microns. After 15 minutes of hypertension, when coronary diameter had returned to baseline values, the constriction of the large artery to serotonin was potentiated (delta D = -89 +/- 33 microns at 5 micrograms/min; -207 +/- 45 microns at 50 micrograms/min; p less than 0.05). Hypertension for 1-5 minutes potentiated constrictor responses of large coronary arteries for at least 2 1/2 hours. Removal of endothelium prevented effects of hypertension on constrictor responses of large arteries to serotonin. Hypertension did not alter constrictor responses to angiotension II (1 and 2.5 micrograms/min) or methoxamine (50 and 100 micrograms/min) or the dilator response to acetylcholine (40 micrograms/min). Acute hypertension altered endothelial morphology. There were small endothelial craters following 10 seconds of hypertension, and disruption of endothelial junctions with leukocyte adherence following 1-15 minutes of hypertension. We conclude that acute hypertension alters constrictor responses of large coronary arteries to serotonin by impairing endothelial function and not by directly affecting vascular smooth muscle. These effects of acute hypertension on vascular reactivity are selective in that they do not involve non-endothelium-dependent agents or the endothelium-dependent agent, acetylcholine. The effect of hypertension also persists long after pressure is restored to normotensive levels.
Authors:
K G Lamping; W P Dole
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  61     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1987 Dec 
Date Detail:
Created Date:  1988-01-12     Completed Date:  1988-01-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  904-13     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Angiotensin II / pharmacology
Animals
Coronary Vessels / drug effects,  pathology,  physiopathology*
Dogs
Endothelium, Vascular / physiopathology*
Female
Hypertension / pathology,  physiopathology*
Kinetics
Male
Methoxamine / pharmacology
Microscopy, Electron
Microscopy, Electron, Scanning
Serotonin / pharmacology*
Time Factors
Vasoconstriction / drug effects*
Grant Support
ID/Acronym/Agency:
HL 01606/HL/NHLBI NIH HHS; HL 33273/HL/NHLBI NIH HHS; HL 36816/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 390-28-3/Methoxamine; 50-67-9/Serotonin; 51-84-3/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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