Document Detail

Signalling across the blood brain barrier by angiotensin II: novel implications for neurogenic hypertension.
MedLine Citation:
PMID:  18443753     Owner:  NLM     Status:  MEDLINE    
Angiotensin II (AngII) is a major culprit in essential hypertension. Based on a genetic rodent model of hypertension, we review here evidence that AngII may signal across the blood brain barrier to affect neuronal circuits within the nucleus tractus solitarii (NTS) of the brainstem, a pivotal region regulating both the baroreceptor reflex and set point control of arterial pressure. We have termed this form of signalling as vascular-neuronal signalling. We describe that the depressant action of AngII in NTS on the baroreceptor reflex is mediated via activation of endothelial nitric oxide synthase (eNOS) releasing NO that promotes release of the inhibitory transmitter-GABA. This could shunt the incoming excitatory baroreceptor afferent traffic impinging on NTS neurones. Chronic studies recording arterial pressure in conscious unrestrained rats using radio-telemetry have revealed that eNOS in NTS plays an endogenous physiological role in the homeostatic regulation of the gain of the cardiac baroreceptor reflex. However, in the spontaneously hypertensive rat, eNOS mRNA was higher (compared to normotensive rats), and its chronic blockade in NTS restored the abnormally depressed cardiac baroreceptor reflex to levels akin to normotensive rats, improved heart rate variability and lowered arterial pressure. Hence, it seems that excessive eNOS activity in NTS of the SHR contributes to the pathological state of this animal model's cardiovascular autonomic nervous system. We speculate on why eNOS activity may be up regulated in the NTS of the SHR and propose that it is a consequence of high cerebral vascular resistance and inadequate blood perfusion of the brainstem.
Julian F R Paton; Sheng Wang; Jaimie W Polson; Sergey Kasparov
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2008-04-29
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  86     ISSN:  0946-2716     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-09     Completed Date:  2008-09-05     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  705-10     Citation Subset:  IM    
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MeSH Terms
Angiotensin II / metabolism*
Blood-Brain Barrier / metabolism*
Hypertension / enzymology,  metabolism*
Signal Transduction*
Solitary Nucleus / enzymology,  metabolism
Grant Support
RG/07/006/23634//British Heart Foundation; //British Heart Foundation
Reg. No./Substance:
11128-99-7/Angiotensin II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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