Endothelin-1 gene expression and vascular hypertrophy in DOCA-salt hypertension compared to spontaneously hypertensive rats.

1. Enhanced endothelin-1 gene expression has been found in blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In this study, the effects of salt, DOCA and the development of hypertension in DOCA-salt hypertensive rats on the expression of the endothelin-1 gene in blood vessels and on vascular hypertrophy were compared in Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR). 2. Increased endothelin-1 mRNA was found by northern blot analysis in the mesenteric arterial bed of DOCA-salt hypertensive rats and DOCA-salt SHR, but not in DOCA or salt-treated SD rats or in SHR, even when blood pressure reached a mean of 211 mmHg in DOCA-treated SHR. 3. Vascular structure was studied in small mesenteric arteries mounted on a wire myograph. The media width to lumen diameter ratio showed a close correlation with systolic blood pressure except in DOCA-salt hypertensive rats and DOCA-salt SHR, in which it was greater than accounted for by the level of blood pressure. Treatment of DOCA-salt hypertensive rats with the combined ETA/ETB endothelin antagonist bosentan lowered blood pressure slightly, but vascular hypertrophy regressed almost completely and any hypertrophy remaining could be explained by the residual elevated blood pressure. 4. In conclusion, SHR do not exhibit enhanced expression of endothelin-1 in blood vessels. DOCA, salt and elevated blood pressure interact to induce increased arterial expression of endothelin-1. Vascular overexpression of the endothelin-1 gene may produce vascular hypertrophy independently of blood pressure elevation.