Endothelin-1 expression in blood vessels of DOCA-salt hypertensive rats treated with the combined ETA/ETB endothelin receptor antagonist bosentan.
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 endothelin 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Larivière
R
R
Clinical Research Institute of Montréal, Université de Montréal, Canada.
Sventek
P
P
Thibault
G
G
Schiffrin
E L
EL
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis; D015347:RNA Probes; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D015347:RNA Probes; D013449:Sulfonamides; D003900:Desoxycorticosterone; D012194:RNA-Directed DNA Polymerase; D000077300:Bosentan