RT Journal Article
SR Electronic
T1 SARS-CoV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.01.438122
DO 10.1101/2021.04.01.438122
A1 Chanawee Hirunpattarasilp
A1 Gregory James
A1 Felipe Freitas
A1 Huma Sethi
A1 Josef T. Kittler
A1 Jiandong Huo
A1 Raymond J. Owens
A1 David Attwell
YR 2021
UL http://biorxiv.org/content/early/2021/04/01/2021.04.01.438122.abstract
AB The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II alone evoked only a small capillary constriction, but evoked a large pericyte-mediated capillary constriction generated by AT1 receptors in the presence of the SARS-CoV-2 receptor binding domain (RBD). The effect of the RBD was mimicked by blocking ACE2. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7). The clinically-used drug losartan inhibited the RBD-potentiated constriction. Thus AT1 receptor blockers could be protective in SARS-CoV-2 infection by reducing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.Competing Interest StatementThe authors have declared no competing interest.