Roles of nitric oxide, nitrite and myoglobin on myocardial efficiency in trout (Oncorhynchus mykiss) and goldfish (Carassius auratus): implications for hypoxia tolerance

Abstract

SUMMARYThe roles of nitric oxide synthase activity (NOS), nitrite and myoglobin (Mb) in the regulation of myocardial function during hypoxia were examined in trout and goldfish, a hypoxia-intolerant and hypoxia-tolerant species, respectively. We measured the effect of NOS inhibition, adrenaline and nitrite on the O 2 consumption rate and isometric twitch force development in electrically paced ventricular preparations during hypoxia, and measured O 2 affinity and nitrite reductase activity of the purified heart Mbs of both species. Upon hypoxia (9% O 2 ), O 2 consumption and developed force decreased in both trout and goldfish myocardium, with trout showing a significant increase in the O 2 utilization efficiency, i.e. the ratio of twitch force to O 2 consumption, suggesting an increased anaerobic metabolism. NOS inhibition enhanced myocardial O 2 consumption and decreased efficiency, indicating that mitochondrial respiration is under a tone of NOS-produced NO. When trout myocardial twitch force and O 2 consumption are enhanced by adrenaline, this NO tone disappears. Consistent with its conversion to NO, nitrite reduced O 2 consumption and increased myocardial efficiency in trout but not in goldfish. Such a difference correlates with the lower O 2 affinity measured for trout Mb that would increase the fraction of deoxygenated heme available to catalyze the reduction of nitrite to NO. Whereas lowaffinity trout Mb would favor O 2 diffusion within cardiomyocytes at high in vivo O 2 tensions, goldfish Mb having higher O 2 affinity and higher nitrite reductase activity appears better suited to facilitate O 2 diffusion and nitrite reduction in the heart during severe hypoxia, a condition particularly well tolerated by this species.

Keeping the heart in balance: the functional interactions of myoglobin with nitrogen oxides

“…The addition of L-arginine decreases O 2 consumption in turtle myocardial preparations, particularly during hypoxia (Misfeldt et al, 2009), indicating that NOS-derived NO decreases the rate of respiration, most likely by interaction with cytochrome c oxidase as known for mammals (Fig.1B) (Gattuso et al, 1999)]; goldfish Carassius auratus and trout Oncorhynchus mykiss [150mmoll -1 ADMA (Pedersen et al, 2010)]; salmon Salmo salar [10mmoll -1 L-NMMA (Gattuso et al, 2002)]; eel Anguilla anguilla [10mmoll -1 L-NIO (Imbrogno et al, 2001)]; Antarctic Trematomus bernacchii and icefish Chionodracus hamatus and Chaenocephalus aceratus [10mmoll -1 L-NIO (Garofalo et al, 2009a)]. (B)Values shown are relative changes vs control (in %) after the addition of nitrite for mouse [100mmoll -1 nitrite (Rassaf et al, 2007) (Pedersen et al, 2010)].…”

Features of nitrogen metabolism in fishes

“…In fish of NO has important regulatory functions, taking part in the management of the cardiovascular system (Hansen and Jensen 2010;Pedersen et al 2010), the homeostatic functions of the gill apparatus (Jensen 2007;Cossins et al 2009), the activity of the cytochrome electron transport chain of mitochondria (Jensen 2007), the reproductive system of fish (Tamanini et al 2003;Tripathi and Krishna 2008). In turn, the process of NO synthesis is regulated by specific enzymatic complexes of NO-synthase, using as a substrate amino acid L-arginine.…”

“…Basic physiological mechanisms of interconversion of NO, nitrite and nitrate in the tissues of fish, in general, coincide with the views on the principles of the functioning cycle of nitric oxide, formulated for higher vertebrates (Reutov et al 1994). The results of recent research show that the intensity of fish nitrite (nitrate)-reductase contour cycle of nitric oxide synthesis may sharply increase in oxygen deficiency (Pedersen et al 2010). It has been suggested that a lack of oxygen stimulates the organ-and species-specific ways to utilize endogenous nitrites to their intracellular accumulation and a more rational use of nitrite reductase chain reaction (Hansen and Jensen 2010;Pedersen et al 2010).…”

“…The results of recent research show that the intensity of fish nitrite (nitrate)-reductase contour cycle of nitric oxide synthesis may sharply increase in oxygen deficiency (Pedersen et al 2010). It has been suggested that a lack of oxygen stimulates the organ-and species-specific ways to utilize endogenous nitrites to their intracellular accumulation and a more rational use of nitrite reductase chain reaction (Hansen and Jensen 2010;Pedersen et al 2010). In addition, the found experimental evidence suggested that exogenous nitrite in fish can also be included in the nitrite reductase circuit synthesis NO (Jensen 2007).…”

Myoglobin's old and new clothes: from molecular structure to integrated function and evolution

“…At the same time, comparative studies on myoglobin function in vertebrates from different environments (Pedersen et al, 2010) (p. 2755) and comparisons with 'natural' knockouts in some amphibians and Antarctic ice fishes are important for mapping out the scale of intraspecific functional diversity of this protein.…”