CHRONIC AT(1) RECEPTOR BLOCKADE ALTERS AORTIC NERVE ACTIVITY IN HYPERTENSION

In the chronic phase of coarctation hypertension (CH) we have shown bo th reduction in baroreceptor sensitivity (Hypertension. 1992;19[suppl II]:II-198-II-201.) and normalization of the depressed baroreceptor re flex control of heart rate, even with the persistence of hypertension in losartan-treated animals (Am J Physiol. 1995;269:H812-H81 8). Tn th e present study we analyzed the effects of angiotensin II blockade on afferent aortic nerve activity of CH and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day PO). CH was ind uced by subdiaphragmatic aortic coarctation, and the treatments lasted 8 days (4 control and 4 experimental days). Aortic pressure (consciou s rats) and aortic nerve activity simultaneous to pressure (anesthetiz ed rats) were recorded on the fourth day of the experimental period. L osartan-treated rats showed reduced tail pressure (104+/-3 versus 117/-3 mm Hg in the vehicle group). In both groups, aortic coarctation ca used a significant increase in pressure (25% and 28%, respectively) an d a depression of the aortic nerve activity/pressure relationship when compared with sham-operated coarcted animals. In the physiological ra nge of pressure changes, the depression was significantly smaller afte r losartan treatment (3.30+/-0.33 versus 2.18+/-0.37%/mm Hg in the los artan- and vehicle-treated CH groups, respectively, versus 5.05+/-0.33 %/mm Hg in the sham-operated vehicle-treated group). Angiotensin type 1 (AT(1)) receptor blockade was also accompanied by reduced variabilit y of the afferent discharge. The data suggested that apart from its pr essure effect, angiotensin II acts at AT(1) receptors to decrease the sensitivity of aortic afferents during physiological (+/-10 mm Hg) inc reases and decreases in pressure. Thus, angiotensin II may contribute to reductions of baroreceptor gain in chronic hypertension.