Nitric Oxide Modulates Intensity of Non-Quantal Acetylcholine Release in Myocardium of the Rat Right Atrium

The main parasympathetic neurotransmitter acetylcholine (ACh) is released in the myocardium from the intramural postganglionic parasympathetic nerve endings. The presence of non-quantal ACh release mechanism has been recently demonstrated in these neurons. Non-quantal ACh release does not depend on exocytosis of ACh-containing vesicles in response to nerve impulse activity but is believed to be mediated by high-affinity choline uptake system. The intensity of non-quantal ACh release in the myocardium correlates with the size of effects of acetylcholinesterase inhibitors inducing accumulation of non-quantal ACh in the myocardium. The present study deals with the influence of putative modulators of non-quantal ACh release nitric oxide (NO) and ATP on the intensity of cholinergic effects induced by organophosphorous acetylcholinesterase inhibitor paraoxon. Intracellular registration of bioelectrical activity in rat isolated right atrium preparation was used. In normal conditions paraoxon (10(-7)-10(-5) M) produced a marked decrease in action potential (AP) duration at the level of 50 and 90% repolarization in the working right atrial myocardium, as well as slowing of the sinus rhythm. ATP, which is known to suppress non-quantal ACh release in the neuromuscular junction, did not induce significant reduction or augmentation of paraoxon (5 x 10(-6) M) effects. Donors of NO, sodium nitroprusside (10(-5) M) and SNAP (10(-4) M) significantly reduced the paraoxon-induced AP shortening. Moreover, sodium nitroprusside decreased the negative chronotropic effect of paraoxon by 43.7%. On the contrary, NO-synthase inhibitor L-NAME (10(-4) M), which is known to suppress endogenous NO production, enlarged the AP shortening caused by paraoxon. In conclusion, NO may be considered as a universal regulator of non-quantal ACh release intensity both in myocardium and in neuromuscular junction.