OBJECTIVE: To investigate the effect of @entity205 ( @entity870 ; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and @entity1372 excretion in healthy volunteers. Furthermore, we studied whether @entity870 enhances the systemic and renal hemodynamic sensitivity to @entity1063 . METHODS: Eighteen healthy volunteers were administered 10 mg/kg @entity870 or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of @entity1091 (CLi) and @entity1372 (CNa) were measured for 8 h after ingestion of the capsules. @entity1063 (2 microg/kg per h) was infused intravenously for 1.5 h into nine subjects. RESULTS: @entity870 increased the MAP by 17+/-2 mmHg. The GFR decreased by 18+/-2% (P < 0.001) and the RVR increased by 37+/-4% (P< 0.001) after ingestion of @entity870 . The @entity870 -induced increase in MAP preceded the @entity870 -induced fall in GFR. The rise in MAP was followed by an early 35+/-8/0 increase in CNa (P < 0.001). At the end of the 8 h study period, CNa decreased by 25+/-7% (P < 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of @entity1372 , whereas the late @entity1372 retention was secondary to the @entity870 -induced fall in GFR. Infusion of @entity1063 increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without @entity870 having any additional effect. CONCLUSION: It was demonstrated that a single oral dose of @entity870 caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that @entity8 and @entity1372 retention are not the initiating events in @entity870 -induced @entity101 . The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to @entity1063 .

XXXX -induced @entity101 and decline in renal function in healthy volunteers.

@entity8 :: ('MESH:D007674', 'Disease') :: ['renal dysfunction'] @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension'] @entity870 :: ('CHEBI:55379', 'Chemical') :: ['CsA'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporine A'] @entity1091 :: ('MESH:D008094', 'Chemical') :: ['lithium'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['Norepinephrine', 'norepinephrine']
@entity205 :: (MESH:D016572,Chemical) :: ['Cyclosporine']
