EFFECT OF ENDOTHELIN ANTAGONISM ON BLOOD-PRESSURE AND VASCULAR STRUCTURE IN RENOVASCULAR HYPERTENSIVE RATS

To investigate the potential pathogenic role of endothelin in blood pr essure 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 structu re to chronic treatment with the endothelin receptor antagonist bosent an was evaluated. One-kidney, one clip (1K,1C) and two kidney, one cli p (2K,1C) Goldblatt hypertensive rats were treated for 2 wk with bosen tan (100 mg . kg(-1). day(-1)) in their chow, and systolic blood press ure was measured by the tail-cuff method. Vascular structure was studi ed in small arteries mounted on a wire myograph. Treatment with bosent an did not result in a significant change in systolic blood pressure o r in the structure of small coronary, renal cortical, mesenteric, or f emoral 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 hypotensi ve responses or regression of vascular hypertrophy during treatment wi th endothelin antagonists in contrast to what is found in deoxycortico sterone acetate salt hypertensive rats, which exhibit very dramatic in creases 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 e ndothelin component in blood pressure elevation in renovascular hypert ension in rats.