MilliporeSigma
  • Home
  • Search Results
  • Angiotensin II Disrupts Neurovascular Coupling by Potentiating Calcium Increases in Astrocytic Endfeet.

Angiotensin II Disrupts Neurovascular Coupling by Potentiating Calcium Increases in Astrocytic Endfeet.

Journal of the American Heart Association (2021-08-31)
Michaël Boily, Lin Li, Diane Vallerand, Hélène Girouard
ABSTRACT

Background Angiotensin II (Ang II), a critical mediator of hypertension, impairs neurovascular coupling. Since astrocytes are key regulators of neurovascular coupling, we sought to investigate whether Ang II impairs neurovascular coupling through modulation of astrocytic Ca2+ signaling. Methods and Results Using laser Doppler flowmetry, we found that Ang II attenuates cerebral blood flow elevations induced by whisker stimulation or the metabotropic glutamate receptors agonist, 1S, 3R-1-aminocyclopentane-trans-1,3-dicarboxylic acid (P<0.01). In acute brain slices, Ang II shifted the vascular response induced by 1S, 3R-1-aminocyclopentane-trans-1,3-dicarboxylic acid towards vasoconstriction (P<0.05). The resting and 1S, 3R-1-aminocyclopentane-trans-1,3-dicarboxylic acid-induced Ca2+ levels in the astrocytic endfeet were more elevated in the presence of Ang II (P<0.01). Both effects were reversed by the AT1 receptor antagonist, candesartan (P<0.01 for diameter and P<0.05 for calcium levels). Using photolysis of caged Ca2+ in astrocytic endfeet or pre-incubation of 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis (acetoxymethyl ester), we demonstrated the link between potentiated Ca2+ elevation and impaired vascular response in the presence of Ang II (P<0.001 and P<0.05, respectively). Both intracellular Ca2+ mobilization and Ca2+ influx through transient receptor potential vanilloid 4 mediated Ang II-induced astrocytic Ca2+ elevation, since blockade of these pathways significantly prevented the intracellular Ca2+ in response to 1S, 3R-1-aminocyclopentane-trans-1,3-dicarboxylic acid (P<0.05). Conclusions These results suggest that Ang II through its AT1 receptor potentiates the astrocytic Ca2+ responses to a level that promotes vasoconstriction over vasodilation, thus altering cerebral blood flow increases in response to neuronal activity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ionomycin, Free Acid, Streptomyces conglobatus - CAS 56092-81-0 - Calbiochem, Ionomycin, Free Acid, Streptomyces conglobatus, CAS 56092-81-0, is a highly specific for divalent cations and more effective than A23187 (Cat. No. 100105) as a mobile ion carrier for Ca2+.