The haemodynamic effects of cyclosporin A in sheep.
1. Cyclosporin A (CyA; 12 mg/kg/day) was infused into six conscious sheep over 5 days to examine the haemodynamic effects of the drug in normal animals. 2. Mean arterial pressure was increased from 73(1) mmHg to 90(4) mmHg (P less than 0.001). There was no change in cardiac output but calculated total peripheral resistance was elevated from 16(1) to 21(2) mmHg min/1 (P less than 0.001) on day 4. 3. There was no change in plasma [Na], but a fall in plasma [K]. Urinary Na excretion decreased. Glomerular filtration rate, filtration fraction, renal blood flow, renal vascular resistance, body weight, plasma renin and blood aldosterone concentration were unchanged. 4. CyA produces an increase in blood pressure in sheep associated with an increase in total peripheral resistance on days 1, 3, and 4, in the absence of changes in renal function. This suggests that CyA hypertension is not simply a consequence of nephrotoxicity.
Howard Florey Institute of Experimental Physiology and Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
J A
JA
Whitworth
E H
EH
Mills
J P
JP
Coghlan
J G
JG
McDougall
M A
MA
Nelson
C D
CD
Spence
J J
JJ
Tresham
B A
BA
Scoggins
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003524:Cyclosporins / Q000633:toxicity*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D003524:Cyclosporins