The sodium retaining effects of cyclosporine.
The effect of chronic cyclosporine administration on volume regulation was studied in mongrel dogs. Dogs received either cyclosporine (20 mg/kg/day p.o.; N = 7) or vehicle (N = 6) while being maintained on a constant sodium diet. Dogs had measurement of baseline vasoactive hormones. Daily sodium excretion was determined. Following eight days of drug administration, dogs were anesthetized, pre-volume expansion data was collected, and dogs underwent a one hour, 10% body weight 0.9% saline volume expansion. Daily sodium balance was +8.6 +/- 2.2 mEq in the cyclosporine group versus 0.4 +/- 1.8 mEq (P less than 0.05) in the control group after 8 days. Prior to acute volume expansion, aldosterone was 22.5 +/- 7.1 ng% in the cyclosporine group versus 4.7 +/- 0.7 ng% in controls (P less than 0.05). ANF was suppressed in the animals receiving cyclosporine. In response to volume expansion, the cyclosporine group demonstrated an attenuation of maximum urine flow by 56%, fractional excretion of sodium by 52%, and electrolyte free water clearance by 75% when compared to controls (P less than 0.05). We demonstrate that chronic cyclosporine administration activates the renin-angiotensin-aldosterone system, suppresses circulating ANF, and results in chronic sodium retention. Additionally, cyclosporine attenuates the natriuretic and diuretic response to acute volume expansion.
Ciresi
D L
DL
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Lloyd
M A
MA
Sandberg
S M
SM
Heublein
D M
DM
Edwards
B S
BS
D000818:Animals; D001810:Blood Volume / Q000502:physiology; D016572:Cyclosporine / Q000633:toxicity*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage
D012982:Sodium, Dietary; D016572:Cyclosporine; D012964:Sodium