Adrenocorticotrophic hormone-induced hypertension in the rat: effects of the endothelin antagonist bosentan.
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 micrograms/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.
Fraser
T B
TB
Department of Medicine, St George Hospital, University of New South Wales, Sydney, Australia.
Mangos
G J
GJ
Turner
S W
SW
Whitworth
J A
JA
D000324:Adrenocorticotropic Hormone; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*; D014867:Water / Q000378:metabolism
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014867:Water; D000324:Adrenocorticotropic Hormone; D000077300:Bosentan