Nitric oxide (NO) is not involved in accentuated antagonism for chronotropy in the isolated mouse atrium.
Nitric oxide (NO) is reportedly involved in accentuated antagonism in the canine blood-perfused sinoatrial (SA) node, and is thought to modulate cholinergic control of heart rate in rabbits. In the present study, we evaluated the involvement of NO in accentuated antagonism in an isolated preparation of both atria from C57BL/6J mice. Isoprenaline (10(-10) M-10(-7) M) had positive chronotropic effects but decreased rather than increased contraction strength. Carbachol (10(-8) M-3x10(-6) M) had a concentration-dependent, negative chronotropic action. In the presence of a submaximal concentration of isoprenaline (30 nM), the same concentration range of carbachol elicited a larger decrease in heart rate than in the absence of isoprenaline. The larger decrease in heart rate (accentuated antagonism) was not modified by the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methylester (L-NAME). Similar results were obtained using ICR strain mice. Isoprenaline increased cAMP content but not cGMP; carbachol in the presence of isoprenaline increased cGMP but had no further effects on cAMP. In the presence of L-NAME, the increase in cGMP elicited by carbachol was attenuated. In the isolated mouse atria, it appears that NO is not involved in accentuated antagonism due to lack of coupling between cGMP signalling and chronotropic function.
Mori
Toyoki
T
First Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi-cho, 771-0192 Tokushima, Japan. to_mori@research.otsuka.co.jp
Hashimoto
Ayako
A
Takase
Hiromichi
H
Kambe
Toshimi
T
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013045:Species Specificity
D002316:Cardiotonic Agents; D009569:Nitric Oxide; D002217:Carbachol; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester