Cyclosporin A and Cremophor-EL augment renal vascular responses to various agonists and nerve stimulation.

Abstract

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.