Document Detail

Effects of continuous infusion of endothelin-1 in pregnant sheep.
MedLine Citation:
PMID:  9403587     Owner:  NLM     Status:  MEDLINE    
Plasma concentration of endothelin-1, a potent vasoconstrictor produced by the vascular endothelium, has been observed to be significantly increased in a number of pathophysiological states, including preeclampsia. In the present study we have evaluated the effects of elevated plasma endothelin-1 in pregnant sheep by continuous exogenous endothelin-1 administration. Nine pregnant ewes (110+/-5 days' gestation) were instrumented for measurements of maternal mean arterial pressure, renal blood flow, and uterine blood flow. After recovery, endothelin-1 was infused intravenously for 4 hours at a dose that was adjusted to raise mean arterial pressure by approximately 20 mm Hg by the end of the first hour (range 5 to 20 ng/kg per minute). Mean arterial pressure, renal blood flow, uterine blood flow, urinary protein excretion, hematocrit, and plasma endothelin-1 concentration were measured hourly, and renal and uterine vascular resistances were calculated. Endothelin-1 produced significant increases (% change from baseline at t=4 hours) in mean arterial pressure (45+/-8%), renal vascular resistance (353+/-66 %), and uterine vascular resistance (59+/-21%). Endothelin-1 also increased microvascular permeability both systemically and within the kidney, as suggested by marked increases in hematocrit (0.27+/-0.01 to 0.32+/-0.01) and urinary protein concentration (0.95+/-0.1 to 7.9+/-3.2 mg/mL per mg creatinine). There was a highly significant correlation (P<.0001) between plasma endothelin-1 and mean arterial pressure, renal vascular resistance, uterine vascular resistance, hematocrit, and urinary protein content in all sheep studied. In addition, plasma endothelin-1 corresponded well with the time course of the changes in cardiovascular parameters and urinary protein excretion observed. These results provide evidence to suggest that elevation of circulating endothelin-1 in pregnant sheep can produce cardiovascular and hemodynamic changes that in many ways resemble the human disease preeclampsia. This supports the hypothesis that endothelial cell damage and/or dysfunction that is associated with increased production of endothelin-1 could directly contribute to the progression of preeclampsia.
S G Greenberg; R S Baker; D Yang; K E Clark
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  30     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-01-08     Completed Date:  1998-01-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1585-90     Citation Subset:  IM    
Department of Obstetrics and Gynecology, College of Medicine, University of Cincinnati, Ohio 45267-0526, USA.
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MeSH Terms
Blood Pressure / drug effects*
Endothelin-1 / administration & dosage,  blood*,  pharmacology*
Hemodynamics / drug effects*,  physiology
Infusions, Intravenous
Pre-Eclampsia / physiopathology
Pregnancy, Animal / drug effects,  physiology*
Regional Blood Flow / drug effects
Renal Circulation / drug effects
Time Factors
Uterus / blood supply
Vascular Resistance / drug effects
Grant Support
Reg. No./Substance:

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

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