| The impact of the endothelin type A receptor on regional endothelin-1 turnover, in particular renal endothelin-1 release, in humans. | |
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MedLine Citation:
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PMID: 20150570 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The endothelin type A (ETA) receptor was studied in six healthy subjects on two occasions with or without an ETA receptor (BQ-123) blockade. At 40 min of either BQ-123 or NaCl infusion, a concomitant infusion of the endothelin-1 (ET-1) precursor, big ET-1, was initiated to augment ET-1 formation. Blood samples were taken from catheters in a peripheral artery, the renal and femoral veins, and the pulmonary artery. Forty minutes of infusion with BQ-123 alone increased heart rate (P<0.001) and cardiac output (CO; P<0.01) and depressed mean arterial blood pressure (P<0.001) and systemic vascular resistance (SVR; P<0.01). During infusion of big ET-1 alone, CO, stroke volume, and renal blood flow decreased (P<0.01), whereas SVR and pulmonary and renal vascular resistance increased (P<0.05). These responses to big ET-1 were abolished or diminished by BQ-123. Renal ET-1 release was threefold higher when big ET-1 infusion was preceded by BQ-123 infusion (P<0.001). Arterial ET-1 concentrations rose to similar levels after big ET-1 infusion (P<0.01) in both trials because of elevated concomitant pulmonary uptake (P<0.05) after ETA blockade. Although there was no net ET-1 leg exchange, leg ET-1 turnover was higher after big ET-1 was preceded by BQ-123. Gene expression of endothelin-converting enzyme 1 and ET-1 in skeletal muscle remained unaltered on both occasions. Our data demonstrate that the level of circulating ET-1 is regulated by ETA receptor-mediated negative feedback. This mechanism seems to be coupled to increased conversion of big ET-1 and is most potent in the kidneys. This emphasizes the important physiological role of ETA receptors in the kidneys, and the lung seems to be mainly a clearing organ for ET-1. |
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Authors:
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Eric Rullman; Thomas Gustafsson; Gunvor Ahlborg |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-11 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 108 ISSN: 1522-1601 ISO Abbreviation: J. Appl. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-03 Completed Date: 2010-10-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 1625-30 Citation Subset: IM |
Affiliation:
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Department of Laboratory Medicine, Division of Clinical Physiology, Karolinska University Hospital, Huddinge 141 86 Stockholm, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Endothelin-1 / metabolism* Humans Kidney / metabolism* Male Metabolic Clearance Rate Receptor, Endothelin A / metabolism* Vasomotor System / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/Receptor, Endothelin A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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