Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism.
The significance of PDE2 on the atrial inotropy was studied in eu- and hyperthyroidism. The contractile force was measured and negative inotropic capacity of N6-cyclopentyladenosine (CPA) was determined on left atria isolated from 8-day thyroxine- or solvent-treated guinea pigs, in the presence or absence of EHNA (adenosine deaminase and PDE2 inhibitor) or NBTI (nucleoside transporter inhibitor). EHNA was administered to inhibit PDE2, while NBTI was used to model the accumulation of endogenous adenosine. The reduction of the contractile force caused by EHNA was smaller in the thyroxine-treated atria than in the solvent-treated samples. Contrary, NBTI induced a decrease in the contractile force without significant difference between the two groups. In addition, EHNA enhanced the efficiency of CPA in thyroxine-treated atria and did not affect it in solvent-treated samples, while the response to CPA was decreased by NBTI in all atria, especially in hyperthyroidism. On the basis of greater retention of the contractile force and sustained/enhanced responsiveness to CPA in the presence of EHNA we conclude that PDE2's inhibition has a significant positive inotropic effect in guinea pig atria and this effect is proven to be augmented in hyperthyroidism.
Gesztelyi
R
R
Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary. gehlru@king.pharmacol.dote.hu
Zsuga
J
J
Hajdú
P
P
Szabó
J Zs
JZ
Cseppento
A
A
Szentmiklósi
A J
AJ
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D046508:Culture Techniques; D006152:Cyclic GMP / Q000494:pharmacology*; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002316:Cardiotonic Agents; C048599:N(6)-cyclopentyladenosine; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D010727:Phosphoric Diester Hydrolases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; C001789:4-nitrobenzylthioinosine; D006152:Cyclic GMP; D000225:Adenine; D000241:Adenosine