Adrenocorticotrophic hormone-induced hypertension in the rat: Effects of the endothelin antagonist bosentan

1. The effects of the endothelin antagonist bosentan on adrenocorticotrophi c hormone (ACTH)-induced hypertension were examined in the conscious male S prague-Dawley rat. 2. In order to confirm endothelin antagonism, 18 rats were randomly divided into two groups: receiving either (i) endothelin-1 (0.125, 0.25, 0.5 and 1 nmol/kg, i.v.); or (ii) endothelin-l at these doses following bosentan (10 0 mg/kg gavage) and mean arterial pressure recorded (study A). Subsequently , 40 male rats (320+/-5 g) were randomly divided into four groups (n = 10): (i) Sham (0.9% saline, s.c.) + 5% acacia gum gavage; (ii) ACTH (500 mu g/k g per day, s.c.) + 5% acacia gum gavage; (iii) Sham injection + bosentan (1 00 mg/kg per day) gavage; or (iv) ACTH + bosentan. Six control days (C1-C6) were followed by 11 treatment days (T0-T10). Systolic blood pressure, wate r intake, urine volume, food intake and bodyweight were measured every seco nd day (study B). 3. Bosentan significantly attenuated the endothelin-1-induced blood pressur e rise at 0.125 nmol/kg (P <0.05), but not at higher doses. 4. Bosentan at a dose which attenuated endothelin-1-induced blood pressure increase had no effect on either blood pressure or metabolic parameters in ACTH-treated rats. 5. These results suggest that endothelin does not play a major role in ACTH -induced hypertension.