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Free radical signaling in the subfornical organ (SFO) is required for the neurometabolic flow coupling dysfunction induced by angiotensin‐II (AngII) hypertension (HTN)
Author(s) -
Iadecola Costantino,
Capone Carmen,
Faraco Giuseppe,
Cao Xian,
Davisson Robin L,
Wang Gang
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1023.19
Subject(s) - angiotensin ii , subfornical organ , cerebral blood flow , medicine , endocrinology , reactive oxygen species , blood pressure , chemistry , biochemistry
HTN disrupts cerebral blood vessels and causes stroke and dementia. In particular, HTN alters the coupling of cerebral blood flow (CBF) with brain metabolism. In AngII “slow pressor” HTN, reactive oxygen species (ROS) in the SFO mediate the blood pressure (BP) elevation. We studied whether ROS in the SFO are also required for the cerebrovascular dysfunction. Neocortical CBF was monitored by a laser‐Doppler probe through a cranial window in anesthetized mice (n=5/group). The CBF rise induced by neural activity (whisker stimulation; WS) was tested after infusion of AngII (600ng/kg/min) or vehicle (V) for 14dd. Ang II elevated mean BP from 70±2 to 92±2 mmHg, increased ROS in the SFO (2.3±0.3 folds; p<0.05), and attenuated the CBF response to WS (V: 23±2; AngII: 12±1±%)(p<0.05). Comparable HTN by phenylephrine (PE) did not alter the CBF response (V: 22±1; PE:23±1%). Adenoviral gene transfer of the ROS scavenger CuZn‐superoxide dismutase to the SFO attenuated the AngII‐induced ROS increase in the SFO (1.1±0.5 folds; p>0.05), prevented the HTN (V: 73±4; AngII: 74±2mmHg) and blocked the CBF dysfunction (V: 21±3; AngII:22±1%). We conclude that the dysfunction in flow‐metabolism coupling induced by slow pressor AngII HTN cannot be attributed to the BP elevation, but requires ROS signaling in the SFO. The effect is likely to involve neurohumoral mechanisms linking the SFO to neurovascular coupling (Supported by HL96571).