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(Hypertension. 2001;38:569.)
© 2001 American Heart Association, Inc.

Neurogenic Factors

Chronic AT₁ Receptor Blockade Alters Autonomic Balance and Sympathetic Responses in Hypertension

Simone M.M.S. Bezerra; Claudia M. dos Santos; Edson D. Moreira; Eduardo M. Krieger; Lisete C. Michelini

Department of Physiology and Biophysics, ICB (S.M.M.S.B., C.M.d.S., L.C.M.) and Heart Institute (E.D.M., E.M.K.), University of São Paulo, São Paulo, SP, Brazil.

Correspondence to Lisete C. Michelini, PhD, Department of Physiology and Biophysics, Institute of Biomedical Sciences, USP, Av. Prof. Lineu Prestes, 1524, 05508-900 Sao Paulo, SP, Brazil. E-mail michelin{at}usp.br

Abstract

Abstract—— In the coarctation hypertension model, we have shown that chronic treatment with losartan causes both normalization of impaired reflex control of heart rate and partial correction of the depressed aortic nerve activity/pressure 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 vehicle or losartan (10 mg/kg per day PO). Hypertension was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 9 days (4 control and 5 experimental days). On day 5, autoregressive power spectral analysis was performed on heart rate recordings made in conscious rats. Other groups were used for sympathetic splanchnic nerve activity recordings made simultaneously with pressure (anesthetized rats) at basal condition and during loading/unloading of baroreceptors. Losartan treatment induced a significant reduction in basal pressure but did not interfere with the development of hypertension (similar pressure increases of 24% and 28% over control values in losartan and vehicle groups, respectively). In vehicle-treated rats, establishment of hypertension was accompanied by a marked change in power spectral density from high- (1.19±0.06 Hz, 33±6%) to low-frequency components (0,42±0.03 Hz, 54±6%), with increased low-frequency–to–high-frequency ratio. When compared with sham-operated vehicle-treated rats, there was also increase in the gain of sympathetic activity/pressure relationship, with displacement of lower plateau toward high levels of sympathetic activity. No changes in the power spectral density and sympathetic activity/pressure relationship were observed when hypertension developed in the presence of chronic angiotensin type 1 (AT₁) receptor blockade. The data suggest that angiotensin II, activated during the establishment of coarctation hypertension, acts via AT₁ receptors to alter sympathovagal balance, facilitating the sympathetic outflow to heart and peripheral circulation during baroreceptors unloading. Data also indicate that the observed effects are not conditioned by preexisting pressure levels.

Key Words: receptors, angiotensin II • losartan • blood pressure • heart rate • hypertension, experimental • rats

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