Human atrial natriuretic peptide suppresses torsades de pointes in rabbits.
BACKGROUND
The increase in inward current, primarily L-type Ca2+ current, facilitates torsades de pointes (TdP). Because human atrial natriuretic peptide (ANP) moderates the L-type Ca2+ current, in our study it was hypothesized that ANP counteracts TdP.


RESULTS
We tested the effect of ANP, guanosine 3', 5'-cyclic monophosphate analogue (8-bromo cGMP) and hydralazine on the occurrence of TdP in a rabbit model. In control rabbits, administration of methoxamine and nifekalant almost invariably caused TdP (14/15). In contrast, ANP (10 microg . kg(-1) . min(-1)) markedly abolished TdP (2/15), whereas hydralazine failed to show a comparable anti-arrhythmic action (10/15). TdP occurred only in 1 of 15 rabbits treated with 8-bromo cGMP. Presence of early afterdepolarization-like hump in the ventricular monophasic action potential was associated with the occurrence of TdP.


CONCLUSIONS
Results suggest that ANP affects TdP in the rabbit model, and that this anti-arrhythmic effect of ANP is not necessarily shared by other vasodilating agents.
Inaba
Hideko
H
Fourth Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan.
Hayami
Noriyuki
N
Ajiki
Kohsuke
K
Sugishita
Yasuyuki
Y
Kunishima
Tomoyuki
T
Yamagishi
Noboru
N
Yamagishi
Satoshi
S
Murakawa
Yuji
Y
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004562:Electrocardiography; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology; D016171:Torsades de Pointes / Q000188:drug therapy* / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D011744:Pyrimidinones; D013566:Sympathomimetics; D014665:Vasodilator Agents; D006830:Hydralazine; C016276:8-bromocyclic GMP; C076259:nifekalant; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D008729:Methoxamine