Cilostamide Potentiates More the Positive Inotropic Effects of (-)-adrenaline Through Beta(2)-adrenoceptors Than the Effects of (-)-noradrenaline Through Beta (1)-adrenoceptors in Human Atrial Myocardium

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2006 Nov 16

PMID 17106669

Citations 22

Authors

T Christ

A Engel

U Ravens

A J Kaumann

Affiliations

Soon will be listed here.

Abstract

Activation of both beta(1)- and beta(2)-adrenoceptors increases the contractility of human atrial myocardium through cyclic AMP-dependent pathways. Cyclic AMP is hydrolised by phosphodiesterases, but little is known about which isoenzymes catalyse inotropically relevant cyclic AMP accumulated upon stimulation of beta-adrenoceptor subtypes. We have compared the positive inotropic effects of (-)-noradrenaline and (-)-adrenaline, mediated through beta(1)- and beta(2)-adrenoceptors, respectively, in the absence and presence of the PDE3 inhibitor cilostamide (300 nM) or PDE4 inhibitor rolipram (1 muM) on human atrial trabeculae from non-failing hearts. Cilostamide, but not rolipram, potentiated the effects of both (-)-noradrenaline and (-)-adrenaline. Cilostamide increased the -logEC(50)M of (-)-adrenaline more than of (-)-noradrenaline (P < 0.05), regardless of whether or not the patients had been chronically treated with beta-blockers. The results are consistent with a greater PDE3-catalysed hydrolysis of inotropically relevant cyclic AMP produced through beta(2)-adrenoceptors than beta(1)-adrenoceptors in human atrium.

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