Endothelin-1 expression in blood vessels of DOCA-salt hypertensive rats treated with the combined ETA/ETB endothelin receptor antagonist bosentan

1995 ◽  
Vol 73 (3) ◽  
pp. 390-398 ◽  
Author(s):  
Richard Larivière ◽  
Pavol Sventek ◽  
Gaétan Thibault ◽  
Ernesto L. Schiffrin
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Receptor Antagonist ◽  
Blood Vessels ◽  
Thoracic Aorta ◽  
Mesenteric Arteries ◽  
Endothelin Receptor ◽  
Hypertensive Rats ◽  
Endothelin 1 ◽  
Wet Weight

In previous studies it has been shown that blood vessels of deoxycorticosterone acetate (DOCA) salt hypertensive rats present significantly higher immunoreactive ET-1 (ir-ET-1) content and increased ET-1 gene expression. DOCA-salt hypertensive rats respond to treatment with the combined ETA/ETB endotheiin receptor antagonist bosentan with lowering of blood pressure. In the present study, we investigated the ir-ET-1 levels and the expression of the ET-1 gene in blood vessels of DOCA-salt hypertensive rats treated or not treated with bosentan. Blood pressure was significantly lower in bosentan-treated rats (185 ± 6 mmHg; 1 mmHg = 133.3 Pa) compared with DOCA-salt hypertensive rats (203 ± 4 mmHg; p < 0.01). Plasma ir-ET-1 concentration was slightly but significantly elevated (p < 0.01) in DOCA-salt hypertensive rats compared with uninephrectomized control rats, and was further increased (p < 0.01) in bosentan-treated rats. The tissue wet weight and ir-ET-1 content of segments of thoracic aorta were significantly increased (p < 0.01) in DOCA-salt hypertensive rats in comparison with control rats, but were similar in bosentan-treated DOCA-salt rats. The abundance of ET-1 mRNA measured by Northern blot analysis in thoracic aorta and the ir-ET-1 content were attenuated by bosentan treatment. Tissue wet weight and ir-ET-1 content in the mesenteric vascular bed were similar in bosentan-treated and -untreated DOCA-salt rats, and were significantly higher in both groups than in control rats (p < 0.01). ET-1 mRNA levels were increased in mesenteric arteries of DOCA-salt hypertensive rats and were further enhanced by bosentan treatment. These data suggest that inhibition of ETA and ETB receptor mediated ET-1 responses by bosentan has a slight but beneficial effect on blood pressure of DOCA-salt hypertensive rats. Chronic blockade of both ET receptors results in increased circulating levels of ET-1 and attenuated ET-1 expression and vascular hypertrophy in aorta but not in the mesenteric vasculature. ET-1 may be involved in the maintenance of elevated blood pressure in DOCA-salt hypertension and perhaps other experimental models of hypertension in the rat in part through a vascular hypertrophic effect.Key words: endothelin-1, endothelin receptor antagonist, aorta, mesenteric arteries, immunoreactive ET-1, preproET-1 mRNA, gene expression.

Effect of endothelin antagonism on blood pressure and vascular structure in renovascular hypertensive rats

1996 ◽  
Vol 271 (1) ◽  
pp. H88-H93 ◽  
Author(s):  
J. S. Li ◽  
L. Knafo ◽  
A. Turgeon ◽  
R. Garcia ◽  
E. L. Schiffrin
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Blood Vessels ◽  
Renovascular Hypertension ◽  
Vascular Structure ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Vascular Hypertrophy ◽  
Endothelin 1

To investigate the potential pathogenic role of endothelin in blood pressure elevation and vascular hypertrophy in renovascular hypertensive rats, which present twofold elevations in endothelin-1 mRNA abundance in blood vessels, the response of blood pressure and vascular structure to chronic treatment with the endothelin receptor antagonist bosentan was evaluated. One-kidney, one clip (1K,1C) and two kidney, one clip (2K,1C) Goldblatt hypertensive rats were treated for 2 wk with bosentan (100 mg.kg-1.day-1) in their chow, and systolic blood pressure was measured by the tail-cuff method. Vascular structure was studied in small arteries mounted on a wire myograph. Treatment with bosentan did not result in a significant change in systolic blood pressure or in the structure of small coronary, renal cortical, mesenteric, or femoral arteries in 1K, 1C or in 2K, 1C hypertensive rats. In conclusion, modest (twofold) elevations of endothelin-1 gene expression in blood vessels in renovascular hypertension are not associated with hypotensive responses or regression of vascular hypertrophy during treatment with endothelin antagonists in contrast to what is found in deoxycorticosterone acetate salt hypertensive rats, which exhibit very dramatic increases in endothelin-1 expression (five-to eightfold) and do respond to endothelin antagonism with blood pressure lowering and regression of vascular hypertrophy. These small elevations of vascular endothelin-1 gene expression thus do not appear to indicate the presence of an endothelin component in blood pressure elevation in renovascular hypertension in rats.

Magnesium supplementation and deoxycorticosterone acetate – salt hypertension: effect on arterial mechanical properties and on activity of endothelin-1

2002 ◽  
Vol 80 (6) ◽  
pp. 553-561 ◽  
Author(s):  
Nathalie Berthon ◽  
Pascal Laurant ◽  
Daniel Hayoz ◽  
Dominique Fellmann ◽  
Hans R Brunner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Carotid Arteries ◽  
Peripheral Resistance ◽  
Mesenteric Arteries ◽  
Lumen Diameter ◽  
Magnesium Supplementation ◽  
Endothelin 1 ◽  
Acetate Salt ◽  
Salt Hypertension

The aim of this study was to show whether the decrease in blood pressure induced by Mg supplementation in deoxycorticosterone acetate – salt (DOCA–salt) hypertensive rats is associated with mechanical modifications of blood vessels and (or) changes in tissular production and (or) vasoconstrictor activity to endothelin-1. DOCA–salt treatment increased blood pressure, media thickness, cross-sectional area, and lumen diameter of carotid arteries. Distensibility and incremental elastic modulus versus stress were not altered in carotid arteries, suggesting that the DOCA–salt vessel wall adapts structurally to preserve its blood pressure buffering capacity. Magnesium supplementation attenuated DOCA–salt hypertension. In comparison with normotensive rats, systolic, mean, and pulse pressures were higher whereas diastolic pressure was not different in Mg-supplemented DOCA-salt rats. Magnesium supplementation did not significantly modify the elastic parameters of carotid arteries. In resistance mesenteric arteries, DOCA–salt hypertension induces an inward hypertrophic remodeling. Magnesium supplementation attenuates wall hypertrophy and increases lumen diameter to the normotensive diameter, suggesting a decrease in peripheral resistance. Magnesium supplementation normalizes the altered vasoconstrictor activity of endothelin-1 in mesenteric arteries and attenuates endothelin-1 overproduction in kidney, left ventricle, and aorta of DOCA-salt rats. These findings suggest that Mg supplementation prevents blood pressure elevation by attenuating peripheral resistance and by decreasing hypertrophic effect of endothelin-1 via inhibition of endothelin-1 production.Key words: hypertension, resistance, distensibility, blood vessels, magnesium.

Increased vascular endothelin-1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats

Metabolism ◽  
2001 ◽  
Vol 50 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Dae Ho Lee ◽  
JongUn Lee ◽  
Dae Gill Kang ◽  
Yun Woong Paek ◽  
Dong Jin Chung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Hypertensive Rats ◽  
Endothelin 1 ◽  
Oxide Synthase

scholarly journals Gene Expression of Endothelin-1 and Endothelin Receptor A on Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment

2010 ◽  
Vol 40 (9) ◽  
pp. 459 ◽  
Author(s):  
Kyoung Ah Lim ◽  
Kwan Chang Kim ◽  
Min-Sun Cho ◽  
Bo En Lee ◽  
Hae Soon Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Endothelin Receptor ◽  
Endothelin 1 ◽  
Endothelin Receptor A
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