Nitric oxide modulates cardiac performance in the heart of Anguilla anguilla.
Nothing is known about the effects of nitric oxide (NO) on cardiac performance in fish. Using an in vitro working heart preparation that generates physiological 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 preload, afterload and heart rate), the effects of cholinergic stimulation and the Frank-Starling response (preload-induced increases in cardiac output at constant afterload and heart rate). The NO synthase (NOS) inhibitors NG-monomethyl-L-arginine (L-NMMA) and L-N5(1-iminoethyl)ornithine (L-NIO), the guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) and Triton X-100, a detergent that damages the endocardial endothelium, all increased stroke volume (VS) and stroke work (WS). In contrast, the endogenous NOS substrate L-arginine, tested before and after treatment with haemoglobin, the NO donor 3-morpholinosydnonimine, tested with and without the superoxide scavenger superoxide dismutase, and the stable cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) decreased VS and WS. Acetylcholine chloride produced a biphasic effect. At nanomolar concentrations, in 34 % of the preparations, it induced a NO-cGMP-dependent positive inotropism that required the integrity of the endocardial endothelium. Pretreatment with Triton X-100 or with NO-cGMP pathway inhibitors (L-NMMA, L-NIO, NG-nitro-l-arginine methyl ester, Methylene Blue and ODQ) abolished the positive effect of acetylcholine. In contrast, at micromolar concentrations, acetylcholine produced a negative effect that involved neither the endocardial endothelium nor the NO-cGMP pathway. Pre-treatment with L-arginine (10(-6 )mol x l(-1)) was without effect, whereas L-NIO (10(-5 )mol x l(-1)) significantly reduced the Frank-Starling response. Taken together, these three experimental approaches provide evidence that NO modulates cardiac performance in the eel heart.
Imbrogno
S
S
Department of Cell Biology, University of Calabria, Italy and Zoological Station 'A. Dohrn', Villa Comunale, I-80121 Naples, Italy.
De Iuri
L
L
Mazza
R
R
Tota
B
B
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000811:Anguilla / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D017830:Octoxynol / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D003902:Detergents; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018727:Muscarinic Antagonists; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010276:Parasympatholytics; D011810:Quinoxalines; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D010890:Pirenzepine; C002385:linsidomine; D001285:Atropine; D017830:Octoxynol; D001120:Arginine; D008981:Molsidomine; D009952:Ornithine; D013482:Superoxide Dismutase; D000109:Acetylcholine; C048593:otenzepad; D019331:NG-Nitroarginine Methyl Ester