THE MECHANISMS OF NO-DEPENDENT CONTROL OF THE CEREBRAL CIRCULATION IN HYPERCAPNIA

Respiratory hypercapnia tests are commonly used for diagnostics and predicting disorders in regulation of the cerebral circulation (CC). However, mechanisms of the hypercapnia effect on CC have been poorly explored, including the involvement of various isoforms of nitric oxide synthase (NOS) in the response. Purpose of the work is to study the role of NOS isoforms in CC regulation in mice breathing gas mixture with 5 % CO2. Effects of isoform-selective NOS inhibitors on the systemic blood pressure (BP) and CC in the normal condition and during hypercapnia were investigated. Experiments were conducted with mice С57Bl/6J narcotized with a Zoletil and xylazine mixture. BP recording via a catheter in the carotid artery showed that inhibition of nNOS (nitroindazol, 7-NI) has no effect on systemic BP, whereas inhibition of eNOS (L-NIO) rises BP to the same level as observed during inhibition of all NOS isoforms with L-NAME. In the next test series, the linear blood velocity was recorded in large veins located in the frontal and parietal cortex regions using the laser speckle contrast imaging; specialized algorithms were used to determine the internal vascular diameters and volume blood flow. Inhibition of nNOS did not change the basal CC level, while inhibition of eNOS resulted in its reduction. The CC response to hypecapnia decreased in the presence of nNOS inhibitor but not eNOS inhibitor. Participation of the NOS isoforms in CC regulation in the hypercapnic condition can depend on their localization in different types of cerebral cells and peculiar reactions of these cells to acidification.