Chronic losartan treatment decreases angiotensin II-mediated facilitation of noradrenaline release in the caudal artery of spontaneously hypertensiverats

Sympathetic activity is modulated by angiotensin II (AII), both at pre- and postsynaptic level in the rat caudal artery. In the spontaneously hyperten sive rat (SHR), this artery receives more dense sympathetic innervation tha n blood vessels of normotensive strains. This fact seems to be linked to th e enhanced presser responses elicited by noradrenaline in SHR. In this work we describe, in the SHR, the effect of a chronic treatment with the angiot ensin II AT(1)-receptor antagonist, losartan, in modulating noradrenergic m echanisms involved in caudal artery contraction. The effect of losartan is compared to that of captopril, given at doses leading to a similar decrease of both arterial blood pressure and left ventricular hypertrophy. The cont ractile response of caudal artery rings induced by endogenous noradrenaline released by low frequency transmural nerve stimulation (TNS) has been stud ied. Under our conditions, TNS (0.5-1 Hz) induced higher contractile respon ses in SHR treated with losartan than in the control and captopril-treated groups. This difference seems to be due to an increase of the postsynaptic effect of noradrenaline (NA) rather than to an increase of noradrenaline re lease from sympathetic endings, since i) DE50 value for NA was lower in los artan-treated SHR than in the other groups, and ii) AII induced a dose-depe ndent increase of TNS-evoked release of radioactivity from caudal artery se gments loaded with [H-3]-NA, in both control and captopril-treated groups b ut had no effect in the losartan-treated group. These results show that chr onic treatment with losartan, although slightly enhancing the presser effec t of NA at postsynaptic level, fully supresses the facilitatory role of AII on NA release. (C) 2000 Elsevier Science Inc. All rights reserved.