EFFECTS OF RAPAMYCIN ON RENAL HEMODYNAMICS, WATER AND SODIUM-EXCRETION, AND PLASMA-LEVELS OF ANGIOTENSIN-II, ALDOSTERONE, ATRIAL, NATRIURETIC PEPTIDE, AND VASOPRESSIN IN PIGS

We have investigated the acute effects of rapamycin on renal hemodynamics, water, sodium and lithium excretion rates, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in 34 Lancaster/Yorkshire female pigs, a breed that has a renal structure/function resembling that of the human kidney. Three different dosages were given over a 1-hr period: dose A, 0.1 mg/kg (n=8); dose B, 0.2 mg/kg (n=8); dose C, 0.4 mg/kg (n=8); and P, placebo vehicle (n=10). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by constant infusion clearance technique using I-125-iothalamate and I-131-hippuran, and hormonal parameters were measured by RIA. Renal hemodynamics, water and sodium excretion rates, and tubular function, evaluated by the lithium clearance technique, were unchanged both during and up to 2 hr after rapamycin infusion, although GFR and RPF increased when rapamycin was given in supratherapeutic dosages of 0.4 mg/kg (GFR: P, 4.4%; A, 7.9%; B, 2.5%; C, 13.3% [P<0.05]; RPF: P, 7.1%; A, 4.9%; B, 3.9%; C, 15.3% [P<0.01], median values). It is concluded that infusion of rapamycin has no acute deleterious effects on renal function in pigs in therapeutic to supratherapeutic dosages.