The failure of nisoldipine to prevent the hypertensive response to cyclosporine A infusion in sheep.
Hypertension and nephrotoxicity are major clinical problems associated with cyclosporine A administration. Sheep rapidly develop hypertension after intravenous administration of cyclosporine A at 6 mg/kg per day over 5 days, and this is associated with a rise in peripheral resistance. Nephrotoxicity is not a feature of cyclosporine A-induced hypertension in this species. This study reports the use of nisoldipine to investigate the role of Ca2(+)-induced smooth muscle contraction in cyclosporine A-induced hypertension in conscious sheep. After 3 control days, nisoldipine at 24 mg/day was infused intravenously alone for 24h (E1), followed by 5 days of nisoldipine plus cyclosporine A (6 mg/kg per day; E2-E6). After 24 h of nisoldipine alone, mean arterial pressure (MAP) was unchanged, heart rate rose from a control value of 60 +/- 2 beats/min to 102 +/- 9 beats/min (P less than or equal to 0.001), calculated total peripheral resistance (CTPR) fell from 15.8 +/- 0.5 to 11.7 +/- 0.5 mmHg/l per min (P less than or equal to 0.001) and stroke volume fell from 73 +/- 4 ml/beat to 60 +/- 5 ml/beat (P less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Tresham
J A
JA
Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Australia.
Whitworth
J A
JA
Scoggins
B A
BA
Bennett
W M
WM
D000818:Animals; D002118:Calcium / Q000502:physiology; D003524:Cyclosporins / Q000097:blood / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D015737:Nisoldipine / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012756:Sheep; D012964:Sodium / Q000652:urine
D003524:Cyclosporins; D015737:Nisoldipine; D012964:Sodium; D012083:Renin; D011188:Potassium; D002118:Calcium