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Diltiazem modulates cyclosporin A induced renal hemodynamic effects but not its effect on plasma endothelin-1.
- Source :
-
Clinical transplantation [Clin Transplant] 1998 Oct; Vol. 12 (5), pp. 363-70. - Publication Year :
- 1998
-
Abstract
- Cyclosporin A (CsA) has been reported to induce major acute renal hypoperfusion that may be antagonised by calcium channel blockers. The vasoconstrictive peptide endothelin-1 (ET-1) has been proposed as a mediator of CsA induced hypoperfusion. We investigated the acute effects of the new CsA formulation (Sandimmun Neoral) in 8 renal transplant patients on triple immunosuppressive therapy before and following slow-release diltiazem treatment in a dose of 90-120 mg b.i.d for 4 weeks. CsA significantly increased mean arterial blood pressure by 6 +/- 2 mmHg (p < 0.05) during the first 3 h after administration. This effect was abolished by diltiazem treatment, also reducing blood pressure by 12 +/- 3 mmHg (p < 0.05) 3-9 h after administration. CsA administration induced a maximum reduction in renal blood flow of 20 +/- 8% (p < 0.05) 5 h after ingestion and a concomitant reduction in glomerular filtration rate of 18 +/- 7% (p < 0.05). The filtration fraction increased by a maximum of 13 +/- 7% (p < 0.05) after 4 h as did the calculated fractional proximal reabsorption by 14 +/- 4% (p < 0.05). All these acute renal effects were abolished by diltiazem administration. Concurrent with the maximum renal hemodynamic effects, plasma ET-1 was elevated with a peak increase of about 40% 4-5 h after CsA ingestion. Diltiazem treatment had no effect on the increase in plasma ET-1 following CsA administration. These findings suggest that CsA induced acute vasoconstriction and renal hypoperfusion are mediated by ET-1 and that diltiazem treatment abolishes these pharmacodynamic effects of CsA despite persistent increase of plasma ET-1 levels.
- Subjects :
- Adult
Aged
Antihypertensive Agents pharmacology
Blood Pressure drug effects
Endothelin-1 physiology
Female
Glomerular Filtration Rate drug effects
Humans
Male
Middle Aged
Vasoconstriction drug effects
Calcium Channel Blockers pharmacology
Cyclosporine pharmacology
Diltiazem pharmacology
Endothelin-1 blood
Immunosuppressive Agents pharmacology
Kidney Transplantation physiology
Renal Circulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0902-0063
- Volume :
- 12
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 9787942