Effect of felodipine on renal haemodynamics and tubular sodium handling after single-dose cyclosporin infusion in renal transplant recipients treated with azathioprine and prednisolone.
A total of 25 renal transplant recipients, treated solely with prednisolone and azathioprine, were investigated in a randomized, double-blind, placebo-controlled, cross-over study. The effect of a single oral dose of felodipine 5 mg or placebo on: glomerular filtration rate (GFR); renal plasma flow (RPF); renal vascular resistance (RVR); renal tubular sodium and water handling, measured by the lithium clearance technique; plasma levels of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF) and arginine vasopressin (AVP); blood pressure (BP), and heart rate (HR) was studied before, during, and after an intravenous infusion of cyclosporin (CyA). Three consecutive clearance periods were performed, each lasting 1 h. During the second period, CyA (0.75 mg kg-1 body weight) was infused. Before infusion of CyA, felodipine caused a significant rise (6.7%) in RPF and lowered RVR, but did not change GFR significantly. The rise in RPF was abolished by infusion of CyA. After infusion, both GFR (7.8%) and RPF (9.4%) were significantly higher and RVR lower after felodipine than after placebo. Proximal tubular output and total sodium excretion were higher on the felodipine day before and after, but not during CyA infusion. In all three periods felodipine reduced both systolic and diastolic BP. In conclusion, a single dose of felodipine increases RPF and decreases blood pressure in renal transplant recipients not treated with CyA. Although some of these changes are abolished by an acute intravenous infusion of CyA, the effects of felodipine are present again also during the 1st hour after the infusion and thereby indicate at least in part some renal protective effect of felodipine. It is suggested that a higher dose of felodipine might also have been preventive against CyA renal side-effects during the acute infusion.
Madsen
J K
JK
Department of Medicine and Nephrology C, Skejby Hospital, University Hospital in Aarhus, Denmark.
Kornerup
H J
HJ
Pedersen
E B
EB
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000494:pharmacology; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D015736:Felodipine / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008094:Lithium / Q000652:urine; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D014665:Vasodilator Agents / Q000494:pharmacology*
D006728:Hormones; D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D016572:Cyclosporine; D008094:Lithium; D012964:Sodium; D011239:Prednisolone; D001379:Azathioprine; D015736:Felodipine