From the Department of Physiology and Biophysics, ICB (C.M.S., L.C.M.),
and the Heart Institute, University of São Paulo (E.D.M., E.M.K.),
São Paulo, Brazil.
Correspondence to Lisete C. Michelini, PhD, Department of Physiology and Biophysics, Institute of Biomedical Sciences, USP, Ave Prof. Lineu Prestes, 1524, 05508–900 São Paulo SP, Brazil. E-mail lisete{at}bmb.icb1.usp.br
Abstract—In the chronic phase of
coarctation hypertension (CH) we have shown both reduction in
baroreceptor sensitivity (Hypertension. 1992;19[suppl
II]:II-198–II-201.) and normalization of the depressed baroreceptor
reflex control of heart rate, even with the persistence of hypertension
in losartan-treated animals (Am J Physiol.
1995;269:H812-H818). In the 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 induced by
subdiaphragmatic aortic coarctation, and the treatments lasted 8 days
(4 control and 4 experimental days). Aortic pressure (conscious rats)
and aortic nerve activity simultaneous to pressure
(anesthetized rats) were recorded on the fourth day of the
experimental period. Losartan-treated rats showed reduced tail
pressure (104±3 versus 117±3 mm Hg in the vehicle group). In
both groups, aortic coarctation caused a significant increase in
pressure (25% and 28%, respectively) and a depression of the aortic
nerve activity/pressure relationship when compared with sham-operated
coarcted animals. In the physiological range of
pressure changes, the depression was significantly smaller after
losartan treatment (3.30±0.33 versus 2.18±0.37%/mm Hg in
the losartan- and vehicle-treated CH groups, respectively,
versus 5.05±0.33%/mm Hg in the sham-operated vehicle-treated group).
Angiotensin type 1 (AT1) receptor blockade was
also accompanied by reduced variability of the afferent discharge. The
data suggested that apart from its pressure effect,
angiotensin II acts at AT1 receptors to
decrease the sensitivity of aortic afferents during
physiological (±10 mm Hg) increases and
decreases in pressure. Thus, angiotensin II may contribute
to reductions of baroreceptor gain in chronic hypertension.
© 1998 American Heart Association, Inc.
Scientific Contributions
Chronic AT1 Receptor Blockade Alters Aortic Nerve Activity in Hypertension
Key Words: baroreceptors • angiotensin II • receptors, angiotensin • blood pressure • losartan • hypertension, coarctation
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