title: Mechanisms of ciclosporin A-induced vasoconstriction in the isolated perfused rat kidney.
abstract: Hypertension is a well-known side effect of ciclosporin A (CsA). In the present study the mechanisms of vasoconstriction in renal vessels were examined in the isolated perfused rat kidney. Kidneys were perfused with constant flow at a temperature of 37 degrees C with Tyrode's solution equilibrated with 95% O2/5% CO2. CsA was dissolved in ethanol. 500 and 2000 ng/ml increased resistance of renal vessels by 0.97 +/- 0.55 x 10(5) and 2.29 +/- 1.33 x 10(5) dyn s cm-5, respectively (mean values +/- SD, n = 12). The vasoconstriction developed gradually over 4 min. The vasopressor effect of CsA was not changed by saralasin (10(-6) M), nifedipine (10(-6) M) and ketanserin (10(-6) M), but was completely blocked by phentolamine and prazosin (each 10(-6) M). CsA-induced vasoconstriction was not prevented by perfusion with Ca(2+)-free solution containing 2 mmol EGTA. Similarly, pretreatment with reserpine to deplete sympathetic nerve endings from catecholamines did not affect CsA-induced vasoconstriction. The findings suggest that CsA-induced vasoconstriction is mediated by stimulation of alpha 1-receptors. Ca2+ influx does not play a role for CsA-induced vasoconstriction. Prolonged perfusion of rat kidneys with the vehicle cremophor EL elicits an irreversible increase in perfusion pressure.
authors.affiliation: Medizinische Universitätspoliklinik, Münster, BRD.
authors.forename: N
authors.initials: N
authors.lastname: Mehring
authors.forename: K H
authors.initials: KH
authors.lastname: Neumann
authors.forename: K H
authors.initials: KH
authors.lastname: Rahn
authors.forename: W
authors.initials: W
authors.lastname: Zidek
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D016572:Cyclosporine