For such a small molecule, nitric oxide (NO) punches well above its weight. As a key signalling molecule in cardiovascular regulation, it plays a major role in protecting organisms from hypoxia by triggering vasodilatation when oxygen levels fall too low. Although many fish experience hypoxia on a daily basis, Frank Jensen from the University of Southern Denmark explains that little was known about nitric oxide levels in fish and how the molecule responds to hypoxia. However, measuring nitric oxide levels is notoriously difficult. Nitric oxide is extremely unstable, surviving for as little as 2 ms in some circumstances, so Jensen and his colleague Marie Hansen decided to measure nitric oxide metabolite levels in a champion of hypoxia tolerance – the goldfish – to find out how nitric oxide levels respond to normal and hypoxic conditions (p. 3593).
Measuring nitrite, nitrate, S- and N-nitroso compound and Fe-nitrosyl compound levels in seven different goldfish tissues in response to extended periods of normoxia and hypoxia by chemiluminescence, Hansen and Jensen found that the goldfish's nitric oxide metabolite levels were essentially the same as those of normoxic mammals, with blood plasma nitrite levels of 0.75 μmol l–1. Jensen explains that this suggests that the production of nitric oxide by the enzyme nitric oxide synthase is similar in fish and mammals. However, after 2 days of hypoxia things were very different. The goldfish's blood plasma nitrate and nitrite levels had dropped dramatically.
Jensen and Hansen explain that this large drop in nitrate and nitrite levels could be due to two causes. One possibility is that the fish are recycling nitrate and nitrite to produce nitric oxide when oxygen is scarce. Alternatively, nitrate and nitrite levels could be low because the low oxygen levels limit nitric oxide synthesis by nitric oxide synthase.
However, despite the spectacular reductions in nitrate and nitrite levels that Jensen and Hansen found in blood plasma, when they examined these and other nitric oxide metabolites in liver, kidney, heart, brain, skeletal muscle and gill after hypoxia, they found that they were essentially the same in normoxic and hypoxic tissues. Jensen and Hansen suspect that although goldfish net nitrite levels fall during hypoxia, the fish transfers nitrite from extracellular compartments to intracellular compartments to ensure that sufficient nitric oxide is available to regulate cellular function when oxygen is scarce.