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  • Title: 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.
    Author: Golbaekdal K, Nielsen CB, Pedersen EB.
    Journal: J Pharm Pharmacol; 1996 Nov; 48(11):1174-9. PubMed ID: 8961168.
    Abstract:
    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.
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