Cyclosporin A and Cremophor-EL augment renal vascular responses to various agonists and nerve stimulation.
The acute actions of cyclosporin A and its solvent Cremophor-EL on the rise of perfusion pressure induced by periarterial stimulation were studied in the rabbit isolated kidney. Thirty-second stimulations were used and the parameters were 1-25 Hz, 5 msec duration, and 15 V. The responses to periarterial stimulation were frequency-dependent. Noradrenaline (0.01-20 microgram) induced similar effects when given into the renal artery. Clonidine (10(-7)M), added to the perfusion medium, inhibited the responses to periarterial stimulation without altering the effect of noradrenaline. Cyclosporin A (10(-7)-4 x 10(-5)M), added to the perfusion medium, potentiated the responses both to periarterial stimulation and exogenously given noradrenaline and restored the responses to clonidine (10(-7)M). The effects of cyclosporin A and Cremophor-EL on the responses to various contractile agonists (potassium chloride, phenylephrine, serotonin and angiotensin II) were also studied in the rabbit isolated renal artery. The results suggest that cyclosporin A may exert a direct action on the vasculature rather than an action on the vascular adrenergic neurotransmission of the rabbit kidney.
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004357:Drug Synergism; D004558:Electric Stimulation; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000294:innervation / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D014677:Pharmaceutical Vehicles; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000294:innervation; D012079:Renal Circulation / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D014677:Pharmaceutical Vehicles; D013566:Sympathomimetics; C000515:cremophor EL; D016572:Cyclosporine; D005990:Glycerol; D009638:Norepinephrine