Angiotensin II attenuates functional hyperemia in the mouse somatosensory cortex.
We investigated whether angiotensin II (ANG II), a peptide that plays a central role in the genesis of hypertension, alters the coupling between synaptic activity and cerebral blood flow (CBF), a critical homeostatic mechanism that assures adequate cerebral perfusion to active brain regions. The somatosensory cortex was activated by stroking the facial whiskers in anesthetized C57BL/6J mice while local CBF was recorded by laser-Doppler flowmetry. Intravenous ANG II infusion (0.25 mug.kg-1.min-1) increased mean arterial pressure (MAP) from 82 +/- 2 to 102 +/- 3 mmHg (P < 0.05) without affecting resting CBF (P > 0.05). ANG II attenuated the CBF increase produced by whisker stimulation by 65% (P < 0.05) but did not affect the response to hypercapnia or to neocortical application of the nitric oxide donor S-nitroso-N-acetyl penicillamine (P > 0.05). The effect of ANG II on functional hyperemia persisted if the elevation in MAP was offset by controlled hemorrhage or prevented by topical application of the peptide to the activated cortex. ANG II did not reduce the amplitude of the P1 wave of the field potentials evoked by whisker stimulation (P > 0.05). Infusion of phenylephrine increased MAP (P > 0.05 from ANG II) but did not alter the functional hyperemic response (P > 0.05). The data suggest that ANG II alters the coupling between CBF and neural activity. The mechanisms of the effect are not related to the elevation in MAP and/or to inhibition of the synaptic activity evoked by whisker stimulation. The imbalance between CBF and neural activity induced by ANG II may alter the homeostasis of the neuronal microenvironment and contribute to brain dysfunction during ANG II-induced hypertension.
Kazama
Ken
K
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 E. 69th Street, Rm. KB410, New York, NY 10021, USA.
Wang
Gang
G
Frys
Kelly
K
Anrather
Josef
J
Iadecola
Costantino
C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006940:Hyperemia / Q000188:drug therapy*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010656:Phenylephrine / Q000494:pharmacology; D010812:Physical Stimulation; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014738:Vibrissae / Q000502:physiology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine