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- Title
ADRENOCORTICOTROPHIC HORMONE-INDUCED HYPERTENSION IN THE RAT: EFFECTS OF THE ENDOTHELIN ANTAGONIST BOSENTAN.
- Authors
Fraser, Tafline B; Mangos, George J; Turner, Steven W; Whitworth, Judith A; Whitworth, Ja
- Abstract
1. The effects of the endothelin antagonist bosentan on adrenocorticotrophic hormone (ACTH)-induced hypertension were examined in the conscious male Sprague-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-1 at these doses following bosentan (100 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 μg/kg per day, s.c.) + 5% acacia gum gavage; (iii) Sham injection + bosentan (100 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, water intake, urine volume, food intake and bodyweight were measured every second day (study B). 3. Bosentan significantly attenuated the endothelin-1-induced blood pressure 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.
- Subjects
ENDOTHELINS; HYPERTENSION; THERAPEUTICS; ADRENOCORTICOTROPIC hormone; EXPERIMENTAL pharmacology; PHYSIOLOGY; CHEMICAL inhibitors
- Publication
Clinical & Experimental Pharmacology & Physiology, 1999, Vol 26, Issue 8, p628
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1046/j.1440-1681.1999.03101.x