title: Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression.
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.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Carine T
authors.initials: CT
authors.lastname: Sangaleti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Crescenzi
authors.forename: Lisete C
authors.initials: LC
authors.lastname: Michelini
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000808:Angiotensinogen / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D001933:Brain Stem / Q000378:metabolism*; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D017552:Solitary Nucleus / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D000804:Angiotensin II; D019808:Losartan