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(Hypertension. 2004;43:317.)
© 2004 American Heart Association, Inc.

Scientific Contribution

Endogenous Angiotensin and Pressure Modulate Brain Angiotensinogen and AT_1A mRNA Expression

From the Department of Physiology and Biophysics, Institute of Biomedical Sciences, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

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

In the coarctation hypertension model, we showed both dissociation of plasma renin activity from cardiovascular-induced effects and the reversal of hypertension-induced responses by losartan. In this study, we investigated the effects of hypertension on the expression of brain renin-angiotensin system components and the simultaneous functional responses and effects of long-term angiotensin II (AT) receptor blockade on these responses. Rats were given vehicle or losartan for 9 days and subjected to subdiaphragmatic aortic constriction or sham surgery after 4 days of treatment. On the fifth postsurgical day, pressure and heart rate were measured in the conscious state; the brain was perfused and removed afterward. Sequential slices of brainstem were hybridized with ³⁵S-oligodeoxynucleotide probes for angiotensinogen, AT_1A, and AT_1B receptors and processed for autoradiography and densitometry. In vehicle-treated rats, hypertension was accompanied by tachycardia and marked increments in angiotensinogen and AT_1A mRNA expression in the cardiovascular system–controlling brainstem areas. In the nucleus tractus solitarii, AT_1A density was correlated with both pressure and heart rate values (P<0.01), whereas angiotensinogen levels were correlated with pressure only (P<0.05). Losartan did not change the pressure of hypertensive rats (142±4 versus 146±2 mm Hg, losartan versus vehicle) and the hypertension-induced angiotensinogen mRNA expression but did block both tachycardic response and hypertension-induced AT_1A mRNA expression. Hypertension and losartan did not change AT_1B mRNA expression. The hypertension-induced positive feedback on angiotensinogen and AT_1A mRNA expression supports the concept of a permissive role for brain angiotensin II in orchestrating circulatory responses during the development of hypertension. These data also explain the efficacy of long-term AT₁ receptor blockade to reverse hypertension-induced effects.

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

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