RESUMO
The renin-angiotensin system (RAS) has been identified as an attractive target for the treatment of stress-induced cardiovascular disorders. The effects of angiotensin (ANG) peptides during stress responses likely result from an integration of actions by circulating peptides and brain peptides derived from neuronal and glial sources. The present review focuses on the contribution of endogenous brain ANG peptides to pathways involved in cardiovascular responses to stressors. During a variety of forms of stress, neuronal pathways in forebrain areas containing ANG II or ANG-(1-7) are activated to stimulate descending angiotensinergic pathways that increase sympathetic outflow to increase blood pressure. We provide evidence that glia-derived ANG peptides influence brain AT(1) receptors. This appears to result in modulation of the responsiveness of the neuronal pathways activated during stressors that elevate circulating ANG peptides to activate brain pathways involving descending hypothalamic projections. It is well established that increased cardiovascular reactivity to stress is a significant predictor of hypertension and other cardiovascular diseases. This review highlights the importance of understanding the impact of RAS components from the circulation, neurons, and glia on the integration of cardiovascular responses to stressors.
Assuntos
Angiotensinogênio/metabolismo , Coração/fisiologia , Neuroglia/fisiologia , Sistema Renina-Angiotensina/fisiologia , Estresse Fisiológico/fisiologia , Adaptação Fisiológica/fisiologia , Angiotensinogênio/genética , Animais , Ratos , Ratos TransgênicosRESUMO
Angiotensin-(1-12) [ANG-(1-12)] is a newly identified peptide detected in a variety of rat tissues, including the brain. To determine whether brain ANG-(1-12) participates in blood pressure regulation, we treated male adult (mRen2)27 hypertensive rats (24-28 wk of age) with Anti-ANG-(1-12) IgG or Preimmune IgG via an intracerebroventricular cannula for 14 days. Immunoneutralization of brain ANG-(1-12) lowered systolic blood pressure (-43 +/- 8 mmHg on day 3 and -26 +/- 7 mmHg on day 10 from baseline, P < 0.05). Water intake was lower on intracereroventricular day 6 in the Anti-ANG-(1-12) IgG group, accompanied by higher plasma osmolality on day 13, but there were no differences in urine volume, food intake, or body weight during the 2-wk treatment. In Preimmune IgG-treated animals, there were no significant changes in these variables over the 2-wk period. The antihypertensive effects produced by endogenous neutralization of brain ANG-(1-12) suggest that ANG-(1-12) is functionally active in brain pathways regulating blood pressure.
Assuntos
Angiotensinas/imunologia , Pressão Sanguínea , Encéfalo/metabolismo , Hipertensão/prevenção & controle , Imunoglobulina G/administração & dosagem , Fragmentos de Peptídeos/imunologia , Renina/metabolismo , Angiotensinogênio , Angiotensinas/metabolismo , Animais , Peso Corporal , Modelos Animais de Doenças , Ingestão de Líquidos , Ingestão de Alimentos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Bombas de Infusão Implantáveis , Masculino , Concentração Osmolar , Fragmentos de Peptídeos/metabolismo , Ratos , Ratos Transgênicos , Renina/genética , Fatores de Tempo , UrodinâmicaRESUMO
BACKGROUND: Endogenous angiotensin (Ang)-(1-7) enhances, while Ang II attenuates, baroreceptor sensitivity (BRS) for reflex control of heart rate (HR) in Sprague-Dawley (SD) rats. In (mRen2)27 renin transgenic rats [(mRen2)], there is overexpression of the mouse Ren2 gene in brain, leading to elevated Ang II and reduced Ang-(1-7) in brain medullary, and associated with hypertension and impaired BRS. METHODS: We therefore tested the contribution of endogenous Ang-(1-7) to BRS for control of HR and responses to cardiac vagal chemosensitive afferent fiber activation (CVA) with phenylbiguanide (PBG) in anesthetized SD and (mRen2) 27 rats before and after bilateral nucleus of the solitary tract (nTS) injection of the Ang-(1-7) receptor antagonist (D-Ala7)-Ang-(1-7). RESULTS: (mRen2) 27 rats exhibited a approximately 50% impairment in BRS as compared with SD (P < 0.05). (D-Ala7)-Ang-(1-7) attenuated BRS by approximately 50% in SD rats, but was without effect in (mRen2) 27 rats. (D-Ala7)-Ang-(1-7) did not alter the responses to CVA by PBG (iv bolus) in either strain. There were no differences in the depressor effects of Ang-(1-7) injected into the nTS, nor were levels of mRNA different for angiotensin-converting enzyme, angiotensin-converting enzyme 2, neprilysin, or the mas receptor in medullary tissue from SD versus (mRen2)27 rats. CONCLUSION: Endogenous Ang-(1-7) does not provide tonic input in the nTS to modulate BRS for control of HR in (mRen2)27 rats, which may contribute to impairment of BRS in these animals.
