EVIDENCE FOR AN ANTAGONISTIC ANGIOTENSIN-II ALPHA(2)-ADRENOCEPTOR INTERACTION IN THE NUCLEUS-TRACTUS-SOLITARII

Interactions between alpha(2)-adrenoceptors and angiotensin II recepto rs were evaluated in the nucleus tractus solitarii of the rat by means of quantitative receptor autoradiography and cardiovascular analysis. In binding experiments using l-noradrenaline to compete for [H-3]p-am inoclonidine binding sites, angiotensin II (1 nM) increased the IC50 v alue of l-noradrenaline by 50%. The angiotensin AT(2) receptor antagon ist, DUP753 (losartan), not only blocked this action but also decrease d the IC50 value of l-noradrenaline. The modulatory effect of angioten sin II was also evaluated after addition of both DUP753 and PD123319, an angiotensin AT(2) receptor antagonist, and counteraction of the red uction in the IC50 value of l-noradrenaline was observed. In saturatio n experiments angiotensin II increased the K-D and B-max values of [H- 3]p-aminoclonidine binding sites, compatible with possible uncoupling of the alpha(2)-adrenoceptors. Cardiovascular analysis demonstrated th at a threshold dose of angiotensin II (0.05 pmol) counteracted the vas odepressor effect produced by an ED(50) dose of l-adrenaline, l-noradr enaline or clonidine coinjected in the nucleus tractus solitarii. DUP7 53 fully blocked this in vivo modulation of alpha(2)-adrenoceptors by angiotensin II. These findings suggest the existence of an antagonisti c angiotensin AT(1)/alpha(2)-adrenoceptor interaction in the nucleus t ractus solitarii. Therefore, it can be surmised that the activation of angiotensin II AT(1) receptors may reduce the transduction of the alp ha(2)-adrenoceptors and thus the alpha(2)-mediated vasodepressor respo nses.