Angiotensin II (AngII) induces the expression of suppressor of cytokine signaling (SOCS)-3 in rat hypothalamus - a mechanism for desensitization of AngII signaling

Angiotensin 11 exerts a potent dypsogenic stimulus on the hypothalamus, which contributes to its centrally mediated participation in the control of water balance and blood pressure. Repetitive intracerebroventricular (i.c.v.) injections of angiotensin 11 lead to a loss of effect characterized as physiological desensitization to the pepticle's action. In the present study, we demonstrate that angiotensin 11 induces the expression of suppressor of cytokine signaling (SOCS)-3 via anglotensin receptor 1 (AT1) and JAK-2, mostly, located at the median preoptic lateral and anterodorsal preoptic nuclei. SOCS-3 produces an inhibitory effect upon the signal transduction pathways of several cytokines and hormones that employ members of the JAK/STAT families as intermediaries. The partial inhibition of SOCS-3 translation by antisense oligonucleotide was sufficient to significantly reduce the refractoriness of repetitive i.c.v. angiotensin 11 injections, as evaluated by water ingestion. Thus, by acting through AT1 on the hypothalamus, angiotensin 11 induces the expression of SOCS-3 which, in turn, blocks further activation of the pathway and consequently leads to desensitization to angiotensin 11 stimuli concerning its dypsogenic effect.