Cyclosporin A inhibited the effect of angiotensin II and antidiuretic hormone in osmotic water permeability at the site distal to the generation of cyclic AMP.

SANTOS, J.C., JEREZ, S., PERAL DE BRUNO, M. AND COVIELLO, A.

Buenos Aires

Congreso; XVI International Congress of Nephrology.; 1999

In previous experiments we demosntrated that cyclosporin A (CyA) inhibited the effect of angiotensin II (ang II) and antidiuretic hormone (ADH) in osmotic water permeability (Posm) in toad skin, a tissue with functional properties similar to the distal mammalian nephron. Ang II and ADH in toad skin shares a common receptor and acts through generation of cyclic AMP. The purpose of the present work was to know if this inhibition was before or after generation of cyclic AMP. Posm was measured by a gravimetrical method in paired pieces of isolated pelvic ventral skin of the toad (Bufo arenarum). Results were expressed in mg.cm-2.h-1 as the mean ± S.E. After an equilibration period of one hour control measurements were performed and CyA (0.42 x 10-6 M) was added to the dermal side of one half (experimental) before adding theophylline (THEO), an inhibitor of phosphodiesterase (3.2 x 10-3 M), or dybutyril cyclic AMP (cAMP) (6.3 x 10-3 M) to both halves. CyA at 40 min produced an inhibition of 53.4 % in the response to THEO, control 31.6 ± 8.5, experimental 14.7 ± 6.8, difference 16.9 ± 4.6, N=8, p<0.01. CyA also produced an inhibition of 71.4 % at 20 min of the response to cAMP, control 28.4 ± 5.6, difference 20.5 ± 5.6, N=11, p<0.01. These results demonstrated that CyA inhibits the Posm response to angII and ADH at a site distal to the generation of cAMP probably interfiring with its action on the insertion of water channels in the luminal membrane.