title: Nitric oxide improves the hemodynamic performance of the hypoxic goldfish (Carassius auratus) heart.
abstract: Goldfish tolerate prolonged and severe hypoxia, thus representing a well-suited model to study the maintenance of cardiac function when O(2) availability represents a limiting factor. Using a working heart preparation, we explored the role of the intracardiac nitric oxide synthase (NOS)-derived nitric oxide (NO) under normoxic and hypoxic conditions. Cardiac performance was examined both under basal (constant preload and afterload) and loading conditions, i.e. preload-induced increases in stroke volume (SV) and hence cardiac output at constant afterload (the Frank-Starling response). Hypoxic hearts showed an increased basal mechanical performance compared to the normoxic counterpart. Under basal conditions, in both normoxic and hypoxic hearts, NOS and soluble guanylyl cyclase (sGC) inhibition increased SV, while exogenous NO supply decreased it. The normoxic heart was very sensitive to filling pressure increases; the maximum SV = 1.08 ± 0.09 mL/kg body mass was obtained at 0.4 kPa. Acute hypoxia increased this sensitivity, SV reaching the maximum value (1.45 ± 0.12 mL/kg body mass) at 0.25 kPa. NOS inhibition by L-NMMA reduced the Frank-Starling response under normoxia, but was ineffective under acute hypoxia, where NO may come from nitrite reduction. In both conditions, sGC inhibition induced a reduction of the cardiac response to preload. Moreover, under acute hypoxia, NO scavenging significantly reduced the Frank-Starling response. The hypoxia-induced hemodynamic patterns were complemented by Western blotting analysis which revealed increased expressions of NOS and hypoxia inducible factor α(HIF-1α). In conclusion, we demonstrated that intracardiac NO/NOS enhances goldfish heart performance, remarkably expanding its hypoxic tolerance.
authors.affiliation: Department of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Arcavacata di Rende (CS), Italy. Electronic address: sandra.imbrogno@unical.it.
authors.forename: S
authors.initials: S
authors.lastname: Imbrogno
authors.affiliation: Department of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: C
authors.initials: C
authors.lastname: Capria
authors.affiliation: Department of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: B
authors.initials: B
authors.lastname: Tota
authors.affiliation: Department of Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
authors.forename: F B
authors.initials: FB
authors.lastname: Jensen
mesh_terms: D000818:Animals; D006054:Goldfish; D006439:Hemodynamics; D000860:Hypoxia / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*
chemical_list: D009569:Nitric Oxide
keywords: Cardiac performance; Frank–Starling response; Hypoxia; O(2) availability; Stroke volume