PhD Scientific Days 2020

Theoretical and Translational V. Lectures

Relevance of Nitric Oxide and Prostanoid Mediators in the Autoregulation of Cerebrocortical Blood Flow in Mice

Előadó neve

Hricisák, László, MSc

Előadó munkahelye

Semmelweis University, Institute of Translational Medicine

Előadó telefonszáma

+36-20/5442491

Előadó e-mail címe

laszlo.hricisak@gmail.com

Az előadás címe

Relevance of Nitric Oxide and Prostanoid Mediators in the Autoregulation of Cerebrocortical Blood Flow in Mice

Szerző(k) neve és munkahelye

László Hricisák1, Éva Pál1, Gergely Tamás Izsa1, Andreas Polycarpou1,2, Laura Simoes Dobrydnio1, Nikolett Jabronka1, Éva Ruisanchez1, Ágnes Fülöp1, Zoltán Benyó1
1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2Department of Surgery, Mayo Clinic, Rochester, MN, USA

Szekció

Theoretical and Translational V. Lectures

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Neurosciences

Összefoglaló szövege

Introduction: The understanding of cerebral autoregulation mechanisms has become of notable importance due to the increased incidence of carotid artery stenosis worldwide. Many debates exist in the scientific literature including the role of endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS) and prostanoid mediators (PMs). According to our previous observations, eNOS does not seem to play an important role in the autoregulation of the cerebrocortical blood flow (CoBF) to unilateral common carotid artery occlusion (CAO) (1).
Aims and Methods: We aimed to analyze the combined lack of eNOS and nNOS and the role of PMs in cerebrovascular autoregulation by analyzing the changes of CoBF with laser-speckle imaging after reducing the cerebral perfusion pressure by unilateral (left) CAO in wild-type (WT), as well as in eNOS/nNOS double knock-out (KO) male mice. The role of PMs was tested by indomethacin administration (1 mg/kg, i.p.) and in thromboxane receptor knock-out (TPR-KO) male mice.
Results: In WT animals CoBF reduction in the left temporal cortex started immediately after CAO, reaching its maximum (-27%) at 6-9 s. Thereafter, CoBF recovered close to the pre-occlusion level within 30 s indicating the activation of regulatory pathway(s). Surprisingly, in eNOS/nNOS double KO animals the acute CoBF reduction after CAO was unaltered in all cerebrocortical regions, but the recovery of CoBF was worsened as compared to controls. Indomethacin treatment resulted in a faster recovery in the temporal region, specifically 9-21 s after the occlusion. In TPR-KO animals, however, the recovery of the CoBF was slightly diminished.
Conclusion: These results indicate that (1) the combined lack of eNOS and nNOS impairs only the subacute phase of the recovery after unilateral CAO and (2) indomethacin treatment results in a faster recovery, probably by inhibiting the release of a vasoconstrictor prostanoid, which is not thromboxane A2.
Grant and financial support: EFOP-3.6.3-VEKOP-16-2017-00009, OTKA K-125174, OTKA K-112964, NVKP_16-1-2016-0042.

1. Polycarpou, A., Hricisak, L., Iring, A., Safar, D., Ruisanchez, E., Horvath, B., Sandor, P., and Benyo, Z. (2016) Adaptation of the cerebrocortical circulation to carotid artery occlusion involves blood flow redistribution between cortical regions and is independent of eNOS. Am J Physiol Heart Circ Physiol 311, H972-H980

Additional Information

Supervisor: Zoltán Benyó
E-mail address: benyo.zoltan@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4809

Start

18:15

End

18:30

Authors (legacy)

László Hricisák1, Éva Pál1, Gergely Tamás Izsa1, Andreas Polycarpou1,2, Laura Simoes Dobrydnio1, Nikolett Jabronka1, Éva Ruisanchez1, Ágnes Fülöp1, Zoltán Benyó1
1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2Department of Surgery, Mayo Clinic, Rochester, MN, USA