The role of nitric oxide in the adaptation of cerebrocortical microcirculation to unilateral common carotid artery occlision
Hricisák László
Theoretical and Translational Medicine
Dr. Kellermayer Miklós
SE Elméleti Orvostudományi Központ, Hári terem I. em.
2024-11-05 12:30:00
The Mechanisms of Normal and Pathologic Functions of the Circulatory System
Dr. Benyó Zoltán
Dr. Benyó Zoltán
Dr. Benkő Rita
Dr. Jósvai Attila
Dr. Nagy Zoltán
Dr. Nardai Sándor
dr. Csekő Csongor
CAS is recognized as a significant risk factor for VCI. The impact of CAS on CBF within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral circulation. This doctoral thesis aimed to test the hypothesis that the impaired availability of NO compromises CBF homeostasis after unilateral CAO. In control animals, a rapid CoBF decrease was observed in the ipsilateral frontal, parietal, and temporal regions after CAO. The decreased blood flow in the frontal and parietal regions can be explained by a stealing effect through pial anastomoses between the territories of MCA and AACA. In our first study, genetic deletion of NOS3 failed to influence cerebrovascular adaptation to unilateral CAO in mice, possibly due to the elevated blood pressure in NOS3 KO animals. However, according to our subsequent results, NOS1 KO mice showed increased tortuosity of pial collateral vessels, and NOS1/3 DKO mice exhibited impaired cerebrocortical blood flow adaptation to CAO, particularly in the subacute phase. Furthermore, L-NAME-treated animals exhibited marked and prolonged hypoperfusion in both the ipsilateral and contralateral hemispheres in the acute phase, confirming the crucial role of NO in compensatory mechanisms following CAO. A novel finding of the present study is that whereas acute pharmacological inhibition of NO synthesis had more severe consequences in the acute phase of adaptation, genetic deletion of NOS1/3 mostly compromised the CBF recovery during the subacute phase. We propose that this difference may be related to compensatory vasoregulatory mechanisms upregulated during chronic NO deficiency and probably explains the milder hypertension in NOS KO compared to L-NAME-treated mice. These compensatory mechanisms may support the CBF recovery during the acute phase of adaptation to CAO, resulting in a less severe phenotype of NOS1/3 DKO than L-NAME-treated mice. In the subacute phase, however, the unfavorable morphological development (increased tortuosity) of the leptomeningeal collaterals and lack of NO-mediated vasodilation together may be responsible for the prolonged hypoperfusion of the brain in NOS1/3 DKO mice.
