The ineffectiveness of the NO-cyclic GMP signaling pathway in the atrial myocardium.
1. This study was performed to determine whether nitric oxide (NO) has direct effects on force of contraction (Fc) in atrial myocardium from rats, rabbits, guinea-pigs, frogs, and man. 2. Glyceryl trinitrate, isosorbide dinitrate, 3-morpholino-sydnonimine hydrochloride (SIN-1), and S-nitroso-N-acetylpenicillamine (SNAP) did not significantly reduce Fc in the various preparations investigated, either given alone or after stimulation of alpha- or beta-adrenoceptors. 3. SNAP did not change the time course of contractions in rat, guinea-pig and human preparations. 4. 8-Bromo-guanosine-3':5'-cyclic monophosphate (8-Br-cyclic GMP) produced a negative inotropic effect in rat, guinea-pig and human atrial preparations and shortened time to peak tension and relaxation time in human preparations. 5. High K+ (85 mmol l-1)-induced contracture in rat heart muscle was reduced by 8-Br-cyclic GMP but not by SIN-1. 6. N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, failed to influence muscarinic effects on Fc or frequency from rat and guinea-pig hearts. 7. We conclude that NO, under the experimental conditions described here, has no direct effects on the heart, although cyclic GMP may be involved in the regulation of myocardial contraction.
Nawrath
H
H
Pharmakologisches Institut, Universität Mainz, Germany.
Bäumner
D
D
Rupp
J
J
Oelert
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016275:Atrial Function; D002217:Carbachol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006157:Guanosine Monophosphate / Q000502:physiology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D011898:Ranidae; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006157:Guanosine Monophosphate; D002217:Carbachol; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine