Chronic AT(1) receptor blockade alters autonomic balance and sympathetic responses in hypertension

In the coarctation hypertension model, we have shown that chronic treatment with losartan causes both normalization of impaired reflex control of hear t rate and partial correction of the depressed aortic nerve activity/ press ure relationship, even with the persistence of hypertension. In the present study, we analyzed the effects of angiotensin II blockade on the efferent pathways of coarcted and sham-operated groups treated chronically with vehi cle or losartan (10 mg/kg per day PO). Hypertension was induced by subdiaph ragmatic aortic coarctation, and the treatments lasted 9 days (4 control an d 5 experimental days). On day 5, autoregressive power spectral analysis wa s performed on heart rate recordings made in conscious rats. Other groups w ere used for sympathetic splanchnic nerve activity recordings made simultan eously with pressure (anesthetized rats) at basal condition and during load ing/unloading of baroreceptors. Losartan treatment induced a significant re duction in basal pressure but did not interfere with the development of hyp ertension (similar pressure increases of 24% and 28% over control values in losartan and vehicle groups, respectively). In vehicle-treated rats, estab lishment of hypertension was accompanied by a marked change in power spectr al density from high- (1.19 +/-0.06 Hz, 33 +/-6%) to low-frequency componen ts (0,42 +/-0.03 Hz, 54 +/-6%), with increased low-frequency-to-high-freque ncy ratio. When compared with sham-operated vehicle-treated rats, there was also increase in the gain of sympathetic activity/pressure relationship, w ith displacement of lower plateau toward high levels of sympathetic activit y. No changes in the power spectral density and sympathetic activity/pressu re relationship were observed when hypertension developed in the presence o f chronic angiotensin type 1 (AT(1)) receptor blockade. The data suggest th at angiotensin II, activated during the establishment of coarctation hypert ension, acts via AT(1) receptors to alter sympathovagal balance, facilitati ng the sympathetic outflow to heart and peripheral circulation during baror eceptors unloading. Data also indicate that the observed effects are not co nditioned by preexisting pressure levels.