PhD Scientific Days 2020

Pharmaceutical Sciences II. Posters

Investigation of the Inotropic and Chronotropic Effect of Newly Synthetized Hypoxanthine-Tricyclano on Ex Vivo Rat Atrial Preparations

Előadó neve

Viczján, Gábor, PhD

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, University of Debrecen

Előadó telefonszáma

+36205622877

Előadó e-mail címe

viczjan.gabor@pharm.unideb.hu

Az előadás címe

Investigation of the Inotropic and Chronotropic Effect of Newly Synthetized Hypoxanthine-Tricyclano on Ex Vivo Rat Atrial Preparations

Szerző(k) neve és munkahelye

Department of Pharmacology and Pharmacotherapy, University of Debrecen

Szekció

Pharmaceutical Sciences II. Posters

Language of the presentation

Hungarian

Section, first choice

Pharmaceutical Sciences

Section, second choice

Clinical Medicine

Összefoglaló szövege

The myocardial adenosinergic mechanisms participated in exerting several protective and reparative effects. Accordingly, the adenosinergic system is a promising target of drug development to treat cardiovascular maladies including ischemic heart disease and arrhythmias. Recently in the Department of Pharmaceutical Chemistry, University of Debrecen, hypoxanthine-tricyclano, a new adenosine analogue has been synthetized. Comparing the structure of adenosine and hypoxanthine-tricyclano, adenine and ribose are substituted with hypoxanthine and a tricyclic moiety derived from morpholino, respectively. In a previous study, we have found that the inotropic effect of hypoxanthine-tricyclano can be inhibited by 8-(p-sulfophenyl)theophylline, an A1 and A2 adenosine receptor antagonist, so this effect appears to be mediated, at least in part, by the A1 adenosine receptor. In the present work, we aimed to examine the inotropic and chronotropic effects of hypoxanthine-tricyclano in rat left and right atria, in comparison with those of adenosine.

The left auricula atrii and the right atrium (keeping the interatrial septum) were isolated from male Wistar rats and mounted at 10 mN resting tension in 10 mL vertical organ chambers containing Krebs solution, oxygenated with 95% O2 and 5% CO2 (36°C; pH=7.4). Left atria were paced (3 Hz, 1 ms, 1-2 V), while right atria worked spontaneously. Concentration-effect (E/c) curves were constructed with adenosine and, after wash-out, with hypoxanthine-tricyclano on all atria. Finally, another E/c curve with adenosine was generated without washing out the hypoxanthine-tricyclano doses administered previously. The atrial contractile force and the right atrial rate were measured.

As it is well-established, adenosine exerted strong negative inotropic effect that was similar on the left and right atria. In contrast, hypoxanthine-tricyclano produced a moderate positive inotropic effect (to a similar degree on the left and right atria) that was surmountable with adenosine. Consistent with their inotropic effects, adenosine caused a considerable negative chronotropic effect (as expected), while hypoxanthine-tricyclano exerted a slight positive chronotropic effect that was surmountable with adenosine. These findings suggest that hypoxanthine-tricyclano is a reversible, orthosteric, partial and inverse agonist for the A1 adenosine receptor.

Additional Information

EFOP-3.6.3-VEKOP-16-2017-00009

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4733

Start

13:01

End

13:04

Authors (legacy)

Department of Pharmacology and Pharmacotherapy, University of Debrecen