Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression

Hypertension. 2004 Feb;43(2):317-23. doi: 10.1161/01.HYP.0000112030.79692.21. Epub 2004 Jan 19.

Abstract

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, AT1A, and AT1B receptors and processed for autoradiography and densitometry. In vehicle-treated rats, hypertension was accompanied by tachycardia and marked increments in angiotensinogen and AT1A mRNA expression in the cardiovascular system-controlling brainstem areas. In the nucleus tractus solitarii, AT1A 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 AT1A mRNA expression. Hypertension and losartan did not change AT1B mRNA expression. The hypertension-induced positive feedback on angiotensinogen and AT1A 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / physiology*
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensinogen / biosynthesis*
  • Angiotensinogen / genetics
  • Animals
  • Blood Pressure
  • Brain Stem / metabolism*
  • Gene Expression
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Losartan / pharmacology
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / biosynthesis*
  • Receptor, Angiotensin, Type 1 / genetics
  • Solitary Nucleus / metabolism

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Angiotensinogen
  • Angiotensin II
  • Losartan