Various phosphodiesterase activities in different regions of the heart alter the cardiac effects of nitric oxide.
The modulation of cardiac functions by nitric oxide (NO) was established. This study examined the influences of phosphodiesterase (PDE) inhibitors on the action of NO in the different regions of the rat heart. NO donor diethylamine nonoate (DEA/NO) (0.1-100 μM) decreased functions of the right atrium. DEA/NO-induced depression of the developed tension of the right atrium was inhibited by [erythro-9-(2-hydroxy-3-nonyl)adenine] (PDE2 inhibitor), augmented by milrinone (PDE3 inhibitor), and upturned by rolipram (PDE4 inhibitor). A DEA/NO-induced decrease in the resting tension was inhibited by vinpocetine (PDE1 inhibitor) and [erythro-9-(2-hydroxy-3-nonyl)adenine] but reversed by rolipram. The decreased sinus rate by DEA/NO was prevented by vinpocetine and rolipram. DEA/NO increased cyclic guanosine monophosphate and cyclic adenosine monophosphate (cAMP) concentrations in the right atrium, and rolipram enhanced increased cAMP level. DEA/NO had no effect on the contraction of the papillary muscle. However, unchanged contraction under DEA/NO stimulation was decreased by vinpocetine, milrinone, and rolipram. DEA/NO increased cyclic guanosine monophosphate concentration but has no effect on cAMP in the papillary muscle. However, in the presence of vinpocetine and milrinone, DEA/NO reduced cAMP level. The PDE5 inhibitor sildenafil has no effect on DEA/NO actions. This study indicates that a variety of PDE activities in different regions of the rat heart shapes the action of NO on the myocardium.
Department of Medical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, Ankara, Turkey. dyilmaz@medicine.ankara.edu.tr
Emine
E
Demirel-Yilmaz
Basar
B
Cenik
Gulnihal
G
Ozcan
Mehmet Kursat
MK
Derici
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009924:Organ Culture Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D016896:Treatment Outcome
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D020889:Rolipram