CHRONIC ENDOTHELIN RECEPTOR ANTAGONIST TREATMENT OF YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The effect of the combined ET(A)/ET(B) 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. Conclusion: Endothelins are not involved in the development of hypertension or vascular hypertrophy and remodelling in young SHR.