INFLUENCE OF SOMATOSTATIN ANALOG (SMS-201-995, OCTREOTIDE) ON BLOOD-PRESSURE IN ADRENOCORTICOTROPIN (ACTH) TREATED RATS - ROLE OF HYPERINSULINEMIA IN ACTH HYPERTENSION

1. The hypothesis that adrenocorticotrophin (ACTH)-induced hypertensio n is a consequence of steroid-induced hyperinsulinaemia was tested usi ng the somatostatin analogue (sandostatin, octreotide) to inhibit insu lin release in Sprague-Dawley (SD) rats (n = 41). 2. Octreotide (20 mu g, twice daily) did not modify blood pressure, plasma glucose, bodywei ght, water and electrolyte balance, or organ weights but inhibited ins ulin secretion in the SD rat. 3. Compared with sham injection, ACTH-tr eated (0.5 mg/kg per day) SD rats showed an increase in blood pressure (sham 111 +/- 4 mmHg; ACTH 140 +/- 5 mmHg on treatment day 10 (P < 0. 01), organ weights, water intake, urine volume, plasma glucose, insuli n and sodium concentrations, and decrease of bodyweight and plasma pot assium concentration. 4. Systolic blood pressure in rats treated with combined octreotide and ACTH was similar to that in rats on ACTH alone . Plasma insulin concentration was lower in octreotide + ACTH treated rats than with ACTH treatment alone. There were no differences in body or organ weights, plasma glucose, water or electrolyte balance. 5. Oc treotide lowered plasma insulin concentration to the normal range but did not modify ACTH-induced hypertension in SD rats. These data do not support the notion that insulin-mediated alterations in blood pressur e are a major mechanism for ACTH-induced hypertension in the rat.