Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth muscle contraction

A. Epstein, A. Beall, J. Wynn, Laura L Mulloy, C. M. Brophy

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background. Cyclosporine immunosuppression for organ transplantation is associated with hypertension and nephrotoxicity. Because the effects of cyclosporine as an immunosuppressant are mediated by the effect of cyclosporine as a phosphatase inhibitor, and phosphatase inhibitors are potent vascular smooth muscle contractile agents, we hypothesized that cyclosporine might induce contraction of the renal artery vascular smooth muscle directly. Methods. Strips of bovine renal, carotid, superior mesenteric, or coronary arteries were obtained fresh from an abattoir. The strips were equilibrated in a muscle bath, and the contractile responses to cyclosporine and FK506 were determined. Results. Cyclosporine (50 to 5000 χ/ml), but not FK506, induced rapidly developing, sustained contractions of renal and coronary artery smooth muscle. The magnitude of the cyclosporine- induced contractions of carotid and superior mesenteric artery smooth muscles was significantly less. The magnitude of renal artery smooth muscle contractions induced by cyclosporine was enhanced in the presence of an intact endothelium. Conclusions. Although these effects occurred in vitro to relatively high doses of cyclosporine, these data suggest that cyclosporine may selectively induce renal artery smooth muscle contraction through activation of the Ca2+ dependent phosphatase (calcineurin) in the smooth muscle, and these contractions may be enhanced by the release of endothelial- derived contracting factors.

Original languageEnglish (US)
Pages (from-to)456-460
Number of pages5
JournalSurgery
Volume123
Issue number4
DOIs
StatePublished - Jan 1 1998

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Tacrolimus
Renal Artery
Muscle Contraction
Cyclosporine
Smooth Muscle
Coronary Vessels
Superior Mesenteric Artery
Vascular Smooth Muscle
Phosphoric Monoester Hydrolases
Abattoirs
Organ Transplantation
Immunosuppressive Agents
Baths
Immunosuppression
Endothelium
Hypertension
Kidney
Muscles

ASJC Scopus subject areas

  • Surgery

Cite this

Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth muscle contraction. / Epstein, A.; Beall, A.; Wynn, J.; Mulloy, Laura L; Brophy, C. M.

In: Surgery, Vol. 123, No. 4, 01.01.1998, p. 456-460.

Research output: Contribution to journalArticle

Epstein, A. ; Beall, A. ; Wynn, J. ; Mulloy, Laura L ; Brophy, C. M. / Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth muscle contraction. In: Surgery. 1998 ; Vol. 123, No. 4. pp. 456-460.
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