This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Whitworth, C. E. Articles by Mullins, J. J. Search for Related Content PubMed PubMed Citation Articles by Whitworth, C. E. Articles by Mullins, J. J.

(Hypertension. 1995;26:925-931.)
© 1995 American Heart Association, Inc.

Articles

Endothelin in the Kidney in Malignant Phase Hypertension

Caroline E. Whitworth; Murielle M. Veniant; John D. Firth; Allan D. Cumming; John J. Mullins

From the Centre for Genome Research, University of Edinburgh (C.E.W., M.M.V., J.J.M.); Institute of Molecular Medicine, John Radcliffe Hospital, Oxford (J.D.F.); and Department of Renal Medicine, Royal Infirmary of Edinburgh (A.D.C.) (UK).

Correspondence to Dr Caroline Whitworth, Centre for Genome Research, University of Edinburgh, West Mains Road, Edinburgh, UK.

Abstract A role for endothelin in malignant phase hypertension has been suggested on the basis of reported increases of circulating plasma immunoreactive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontaneous onset malignant hypertension has been described. Expression of the three genes endothelin-1, endothelin-2, and endothelin-3 was quantified in the kidney by specific RNase protection assays in rats with established malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and in normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were significantly elevated in the group with malignant hypertension compared with the other three groups. For determination of whether endothelin-1–mediated effects were crucial in the transition from benign to malignant phase hypertension, an oral nonspecific combined endothelin-A and endothelin-B receptor antagonist (bosentan) was given to hypertensive rats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conclusion, although increased endothelin-1 mRNA expression was found in kidney tissue from rats developing malignant hypertension, blockade of endothelin-1–mediated effects did not prevent the transition from benign phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a causative role and may simply reflect cellular damage and ischemia.

Key Words: endothelin • malignant hypertension • kidney • animals, transgenic

This article has been cited by other articles:

				M. Opocensky, H. J. Kramer, A. Backer, Z. Vernerova, V. Eis, L. Cervenka, V. Certikova Chabova, V. Tesar, and I. Vaneckova Late-Onset Endothelin-A Receptor Blockade Reduces Podocyte Injury in Homozygous Ren-2 Rats Despite Severe Hypertension Hypertension, November 1, 2006; 48(5): 965 - 971. [Abstract] [Full Text] [PDF]

				M. Barton, J. J. Mullins, M. A. Bailey, and M. Kretzler Role of Endothelin Receptors for Renal Protection and Survival in Hypertension: Waiting for Clinical Trials Hypertension, November 1, 2006; 48(5): 834 - 837. [Full Text] [PDF]

				I. Vaneckova, H. J. Kramer, A. Backer, Z. Vernerova, M. Opocensky, and L. Cervenka Early Endothelin-A Receptor Blockade Decreases Blood Pressure and Ameliorates End-Organ Damage in Homozygous Ren-2 Rats Hypertension, October 1, 2005; 46(4): 969 - 974. [Abstract] [Full Text] [PDF]

				G. P. Rossi, M. Cavallin, A. S Belloni, G. Mazzocchi, G. G Nussdorfer, A. C Pessina, and S. Sartore Aortic smooth muscle cell phenotypic modulation and fibrillar collagen deposition in angiotensin II-dependent hypertension Cardiovasc Res, July 1, 2002; 55(1): 178 - 189. [Abstract] [Full Text] [PDF]

				G. P. Rossi, A. Sacchetto, D. Rizzoni, S. Bova, E. Porteri, G. Mazzocchi, A. S. Belloni, M. Bahcelioglu, G. G. Nussdorfer, and A. C. Pessina Blockade of Angiotensin II Type 1 Receptor and Not of Endothelin Receptor Prevents Hypertension and Cardiovascular Disease in Transgenic (mREN2)27 Rats via Adrenocortical Steroid-Independent Mechanisms Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 949 - 956. [Abstract] [Full Text] [PDF]

				S.M Gardiner and T Bennett Comment on "Interactions between endothelin-1 and the renin-angiotensin-aldosterone system" Cardiovasc Res, November 1, 1999; 44(2): 449 - 449. [Full Text] [PDF]

				G. P. Rossi and A. C Pessina Endothelin-1 in angiotensin II-dependent hypertension: Answer to the Letter to the Editor Cardiovasc Res, November 1, 1999; 44(2): 450 - 451. [Full Text] [PDF]

				G. P. Rossi, A. Sacchetto, M. Cesari, and A. C Pessina Interactions between endothelin-1 and the renin-angiotensin-aldosterone system Cardiovasc Res, August 1, 1999; 43(2): 300 - 307. [Abstract] [Full Text] [PDF]