Chronic endothelin receptor antagonist treatment of young spontaneously hypertensive rats.
OBJECTIVE
The effect of the combined ETA/ETB endothelin receptor antagonist bosentan was evaluated in 4-week-old spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats, which were treated for 10 weeks, to determine whether endothelins were involved in the development of hypertension or cardiovascular remodeling in young SHR.


METHODS
Four-week-old SHR and WKY rats received bosentan 100 mg/kg per day mixed with their food. Blood pressure was measured by the tail-cuff method every 2 weeks. At 14 weeks of age the coronary, renal, mesenteric and femoral small arteries were examined on a wire myograph.


RESULTS
The blood pressure both of SHR and of WKY rats was identical in bosentan-treated and untreated rats throughout the study. The media width, lumen diameter, media width:lumen diameter ratio and media cross-sectional area of small arteries of the four vascular beds examined were similar in bosentan-treated and untreated SHR, as were the wet weights of aorta segments and the mesenteric vascular bed.


CONCLUSIONS
Endothelins are not involved in the development of hypertension or vascular hypertrophy and remodelling in young SHR.
Li
J S
JS
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Schiffrin
E L
EL
D000818:Animals; D001158:Arteries / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D006973:Hypertension / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan