Nitric oxide modulates cardiac performance in the heart of Anguilla anguilla

Nothing is known about the effects of nitric oxide (NO) on cardiac performa nce in fish. Using an irt vitro working heart preparation that generates ph ysiological values of output pressure, cardiac output and ventricular work and power, we assessed the effects of NO on the cardiac performance of the eel Anguilla anguilla, We examined basal cardiac performance (at constant p reload, afterload and heart rate), the effects of cholinergic stimulation a nd the Frank-Starling response (preload-induced increases in cardiac output at constant afterload and heart rate). The NO synthase (NOS) inhibitors N- G-monomethyl-L-arginine (L-NMMA) and L-N-5(1-iminoethyl)ornithine (L-NIO), the guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3a)quinoxalin-1-one (ODQ) and Triton X-100, a detergent that damages the endocardial endotheli um, all increased stroke volume (V-S) and stroke work (W-S), In contrast, t he endogenous NOS substrate L-arginine, tested before and after treatment w ith haemoglobin, the NO donor 3-morpholinosydnonimine, tested with and with out the superoxide scavenger superoxide dismutase, and the stable cGMP anal ogue 8-bromoguanosine 3 ' ,5 ' -cyclic monophosphate (8-Br-cGMP) decreased V-S and W-S. Acetylcholine chloride produced a biphasic effect. At nanomola r concentrations, in 34 % of the preparations, it induced a NO-cGMP-depende nt positive inotropism that required the integrity of the endocardial endot helium, Pretreatment with Triton X-100 or with NO-cGMP pathway inhibitors ( L-NMMA, L-NIO, N-G-nitro-L-arginine methyl ester, Methylene Blue and ODQ) a bolished the positive effect of acetylcholine, In contrast, at micromolar c oncentrations, acetylcholine produced a negative effect that involved neith er the endocardial endothelium nor the NO-cGMP pathway. Pre-treatment with L-arginine (10(-6) mol l(-1)) was without effect, whereas L-MO (10(-5) mol l(-1)) significantly reduced the Frank-Starling response. Taken together, t hese three experimental approaches provide evidence that NO modulates cardi ac performance in the eel heart.