Abstract:

Abstract:Objective  To investigate the effects of phosphodiesterase inhibitors (PDEI) on atrial dynamics induced by  C-type natriuretic peptide (CNP) and the contents  of cyclic nucleotide (cAMP,cGMP) in isolated beating rabbit atria.Methods  After the rabbits had been anesthetized,the hearts were  removed rapidly.The left auricles were isolated and fixed on the atrial perfusion system.The atrial stroke volume and the pulse pressure were observed by CNP with or without PDEIs pretreatment.The contents of cAMP and cGMP were measured by radioimmunoassay.Results  ①Compared with control cycle group,CNP (30.0 nmol/L) obviously decreased the atrial stroke volume and pulse pressure (P<0.01) and increased the cGMP content(P<0.001),while the content of cAMP had no change (P>0.05). ②Compared with control cycle group,IBMX (1000.0 nmol/L),a non-selective inhibitor of PDE,significantly increased the atrial stroke volume,pulse pressure,cAMP and cGMP contents (P<0.001),but there were no differences  of the indexes mentioned above between  IBMX (1 000.0 nmol/L)　 plus CNP (30.0 nmol/L)group and IBMX group (P>0.05).③Compared with control cycle group,EHNA (30.0 nmol/L),an inhibitor of PDE2,obviously decreased the atrial stroke volume and pulse pressure (P<0.05) and cAMP content had no change (P>0.05).EHNA (30.0 nmol/L) plus CNP (30.0 nmol/L) showed similar roles with EHNA only.④   Compared with control cycle group,milrinone (1.0 nmol/L),an inhibitor of PDE3,significantly increased the content of cAMP (P<0.05) and slightly increased the atrial stroke volume and pulse pressure,but had no significant differences (P>0.05).CNP (30.0 nmol/L) obviously decreased the atrial stroke volume and pulse pressure (P<0.001),and increased the cAMP content (P<0.05) by pretreatment of milrinone. Compared with milrinone group,milrinone plus CNP decreased the atrial stroke volume and pulse pressure (P<0.001),and the cAMP content had no change(P>0.05).Conclusion CNP can inhibit atrial dynamics by increasing the content of cGMP,the different inhibitors of PDEs play different roles in the CNP-induced inhibition of atrial dynamics in isolated beating rabbit atria.

Key words: atrial natriuretic；phosphodiesterase；heart atria；cyclic nucleotide