Carotid artery stenosis (CAS) affects approximately 5–7.5% of older adults and is
recognized as a significant risk factor for vascular cognitive impairment (VCI). The
impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies
on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed
to test the hypothesis that the impaired availability of nitric oxide (NO) compromises
CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this,
three mouse models exhibiting compromised production of NO were tested: NOS1 knockout,
NOS1/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional
CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI).
Our findings demonstrated that NOS1 knockout, NOS1/3 double knockout, and L-NAME-treated
mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of
one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting
the frontoparietal and temporal regions. In conclusion, our study highlights the significant
contribution of NO production to the functional adaptation of cerebrocortical microcirculation
to unilateral CAO. We propose that impaired bioavailability of NO contributes to the
impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution
after unilateral disruption of carotid artery flow.
