The acute effects of FK-506 on renal haemodynamics, water and sodium excretion and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in pigs.
FK-506 has been shown to be an effective immunosuppressive drug with possible nephrotoxic side effects. In this study we have investigated the acute effects of FK-506 on renal haemodynamics, water, sodium and lithium excretion rates and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and vasopressin in 29 anaesthetized Lancaster/Yorkshire female pigs. A continuous intravenous infusion was given over a 2-h period to 4 groups: A: 0.075 mg kg-1 (n = 7), B: 0.15 mg kg-1 (n = 8), C: 0.3 mg kg-1 (n = 6) and P: placebo vehicle (n = 8). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125-I-iothalamate and 131-I-hippuran as reference substances. Hormonal parameters were measured by radioimmunoassay. In all three FK-506 groups, fractional lithium excretion was significantly decreased 2 h after FK506 infusion (P: +0.4%, A: -8.8% (P < 0.05), B: -12.9% and C: -11.2% (P < 0.01 for both). Mean arterial blood pressure (MBP) was significantly increased in the two highest dosage groups (B,C) at 2 h of infusion: (MBP; P: +2.9%, A: +3.5%, B: +12.0%, C: +15.3% (P < 0.01 for both). GFR and RPF showed minor and inconsistent changes while all other parameters measured showed similar or no changes. In conclusion, acute infusion of FK-506 to pigs does not change overall renal function significantly, but increases mean arterial blood pressure and decreases fractional excretion of lithium.
Golbaekdal
K
K
Research Laboratory of Nephrology and Hypertension, Skejby Hospital, Aarhus University Hospital, Denmark.
Nielsen
C B
CB
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; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008094:Lithium / Q000652:urine; D011897:Random Allocation; D012964:Sodium / Q000652:urine; D013552:Swine; D016559:Tacrolimus / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood
D007166:Immunosuppressive Agents; D014667:Vasopressins; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D016559:Tacrolimus