| Effects of continuous infusion of endothelin-1 in pregnant sheep. | |
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MedLine Citation:
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PMID: 9403587 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S G Greenberg; R S Baker; D Yang; K E Clark |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 30 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1997 Dec |
Date Detail:
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Created Date: 1998-01-08 Completed Date: 1998-01-08 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1585-90 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, College of Medicine, University of Cincinnati, Ohio 45267-0526, USA. Suzanne.Greenberg@uc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects* Endothelin-1 / administration & dosage, blood*, pharmacology* Female Hematocrit Hemodynamics / drug effects*, physiology Humans Infusions, Intravenous Pre-Eclampsia / physiopathology Pregnancy Pregnancy, Animal / drug effects, physiology* Proteinuria Regional Blood Flow / drug effects Renal Circulation / drug effects Sheep Time Factors Uterus / blood supply Vascular Resistance / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL-49901/HL/NHLBI NIH HHS; HL-51051/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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