We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ngċmin-1ċkg-1 and 3.0 ngċmin-1ċkg-1 angiotensin II for 30 min each; Study B, 1.0 ngċmin-1ċkg-1 and 3.0 ngċmin-1ċkg-1 angiotensin II for 120 min each; Study C, 3.0 ngċmin-1ċkg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ngċmin-1ċkg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ngċmin-1ċkg-1 followed by 3.0 ngċmin-1ċkg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10-9, 10-8, 10-7 mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo.
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Research Article|
March 01 1999
Angiotensin II increases the release of endothelin-I from human cultured endothelial cells but does not regulate its circulating levels
Claudio FERRI;
1University of Rome ‘La Sapienza’, Andrea Cesalpino Foundation, Rome 00161, Italy
Correspondence: Dr C. Ferri.
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Giovambattista DESIDERI;
Giovambattista DESIDERI
1University of Rome ‘La Sapienza’, Andrea Cesalpino Foundation, Rome 00161, Italy
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Roberta BALDONCINI;
Roberta BALDONCINI
1University of Rome ‘La Sapienza’, Andrea Cesalpino Foundation, Rome 00161, Italy
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Cesare BELLINI;
Cesare BELLINI
*Department of Experimental Medicine, University of L'Aquila, L'Aquila 67100, Italy
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Marco VALENTI;
Marco VALENTI
†Department of Internal Medicine, University of L'Aquila, L'Aquila 67100, Italy
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Anna SANTUCCI;
Anna SANTUCCI
†Department of Internal Medicine, University of L'Aquila, L'Aquila 67100, Italy
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Giancarlo DE MATTIA
Giancarlo DE MATTIA
1University of Rome ‘La Sapienza’, Andrea Cesalpino Foundation, Rome 00161, Italy
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Publisher: Portland Press Ltd
Received:
May 20 1998
Revision Received:
September 03 1998
Accepted:
October 07 1998
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (1999) 96 (3): 261–270.
Article history
Received:
May 20 1998
Revision Received:
September 03 1998
Accepted:
October 07 1998
Citation
Claudio FERRI, Giovambattista DESIDERI, Roberta BALDONCINI, Cesare BELLINI, Marco VALENTI, Anna SANTUCCI, Giancarlo DE MATTIA; Angiotensin II increases the release of endothelin-I from human cultured endothelial cells but does not regulate its circulating levels. Clin Sci (Lond) 1 March 1999; 96 (3): 261–270. doi: https://doi.org/10.1042/cs0960261
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