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 125I-iothalamate and 131I-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.
Golbaekdal
K
K
Department of Medicine and Nephrology C, Skejby Hospital, University Hospital of Aarhus, Denmark.
Nielsen
C B
CB
Djurhuus
J C
JC
Pedersen
E B
EB
D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology*; D008094:Lithium / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects*; D011090:Polyenes / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D020123:Sirolimus; D013552:Swine / Q000502:physiology*; D014667:Vasopressins / Q000097:blood*
D007166:Immunosuppressive Agents; D011090:Polyenes; D014667:Vasopressins; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D008094:Lithium; D020123:Sirolimus