PhD Scientific Days 2020

Theoretical and Translational III. Posters

Sphingomyelinase-induced Enhanced Vasorelaxation in Db/db Mice

Előadó neve

Dr. Cecília Rita, Panta

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

+36306023131

Előadó e-mail címe

sokszem@gmail.com

Az előadás címe

Sphingomyelinase-induced Enhanced Vasorelaxation in Db/db Mice

Szerző(k) neve és munkahelye

Cecília Rita Panta, Institute of Translational Medicine, Budapest

Szekció

Theoretical and Translational III. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction: Our group investigate the vascular effects of enhanced sphingomyelinase (SMase) activity in a mouse model of type 2 diabetes mellitus (T2DM) and to gain understanding of the secondary signaling pathways involved.
Aims: We aimed to examine the vasoactive effects of of sphingomyelinase (nSMase) on vascular tone in wild-type (WT) and diabetic (db/db) mice.
Method: Our experiments were performed on the thoracic aorta prepared from adult male WT and db/db mice with wire myograph. In experiments, nSMase (0.2 U /ml), eNOS inhibitor L-NAME (100 µM), selective TP receptor antagonist SQ 29,548 (SQ) (1 µM) and for the examination of NO sensitivity of smooth muscle nitroprusside sodium (SNP) (0.1 nmol / l - 10 μmol / l) was used.
Results: Application of nSMase evoked a complex vascular effect both WT and db/db group. Following precontraction with phenylephrine (PE), nSMase resulted in further contraction in WT vessels. In contrast, after the initial vasorelaxation by nSMase the vascular tone showed a slight increase in db/db vessels. Thus, in db/db vessels, in addition to relaxation, there was a delayed and transient vasoconstriction response too. The vasoconstrictive response in time was similar to that observed in WT vessels but it was less. We aimed to isolate the constrictor and the relaxant components of nSMase-induced changes in vascular tone. The TP receptor antagonist SQ was administered 30 minutes before treatment with nSMase. Blocking the TP receptor not only eliminated vasoconstriction, but the subsequent nSMase treatment induced vasorelaxation in both db/db and WT vessels. This vasorelaxation was significantly higher in db/db group. Finally, we investigated the mechanism of nSMase-induced enhanced vasorelaxation in db/db vessels. This may be due to an eNOS-mediated vasorelaxation or a NO-independent mechanism. Co-administration of the nitric oxide synthase (NOS) inhibitor L-NAME abolished the vasorelaxation in both groups.
Conclusion: These results show that the same pathways - namely the TP-mediated vasoconstriction and the a NO-mediated vasorelaxation - mediate the vasoactive effects of nSMase both under physiological conditions (control group) and in pathophysiological conditions (T2DM).

Additional Information

Supervisior: Zoltán Benyó; Éva Ruisanchez
benyo.zoltan@med.semmelweis-univ.hu
ruisanchez.eva@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4786

Start

11:16

End

11:19

Authors (legacy)

Cecília Rita Panta, Institute of Translational Medicine, Budapest