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Adrenocorticotrophin (ACTH) administration has been systematically studied in man and sheep. It raises systolic blood pressure (SBP) in the rat, but this has been little studied. ACTH was injected once daily at 0.5 mg/kg for 12 days in male Sprague-Dawley rats (n=19). Sham-injected animals were studied in parallel (n=15). ACTH increased SBP from 94 ± 4 to 121 ± 4mmHg (P < 0.001), significantly greater (P < 0.02) than sham injection. The SBP of ACTH-treated rats was significantly higher than that of sham-injected rats when the same animals were measured by both the tail-cuff method (ACTH, 126 ± 3mmHg; sham, 99 ± 3 mmHg) and direct arterial cannulation (ACTH, 137 ± 2 mmHg; sham, 123 ± 3 mmHg): P<0.005 and P<0.001, respectively. There was a loss of body weight, and increased water intake and urine output in ACTH-treated animals compared with both control (P < 0.001) and sham treatments (P < 0.02). ACTH increased plasma [Na] (sham, 140 ± 1 mmol/l; ACTH, 145 ± 1 mmol/l; P < 0.001) and urinary Na excretion compared with control (P < 0.01) and sham injection (P < 0.05), and also decreased plasma [K] (sham, 4.6 ± 0.2 mmol/l; ACTH, 3.3 ± 0.8 mmol/l; P < 0.01) and increased urinary K excretion (P < 0.01) compared with control. SBP in adrenalectomized animals (n=10) was unchanged by ACTH. ACTH increased adrenal, renal, cardiac and brain weights compared with sham injection (P < 0.05). There were no significant changes in vascular morphology, although ACTH treatment increased glomerular epithelial cell droplets and abolished the adrenal zona glomerulosa.