Nitric oxide (NO) has proved to be the regulatory molecule of the last decade. Since its identification as the Endothelium Derived Relaxation Factor our love affair with NO has continued with intensity, the number of citations rocketing from a lowly 120 in 1987, to over 5500 last year!
NO is a key modulator of mammalian heart function. It mediates its function through a variety of molecular mechanisms, including regulating cGMP production, by targeting guanylyl cyclase. NO is produced in tissue by nitric oxide synthase (NOS), which uses arginine and oxygen to produce NO. Tinkering with NOS is a good way to find out where NO is regulating a response.
One of the main sources of NO in myocardial tissue is the endocardial endothelium. Fish have a larger ventricle surface area to volume ratio than homeothermic hearts. So, the endocardial endothelium is a potentially rich source of NO for the fish heart. Sandra Imbrogno and colleagues at the University of Calabria decided to investigate whether NO regulation of myocardial function might also be significant in fish, and added the eel Anguilla anguilla to the list of august organisms that have ‘lost their hearts' to NO.
Imbrogno took isolated eel hearts and tested the response to NO under three sets of conditions. Firstly, she looked at the heart under basal conditions and established that NO altered the heart beat under a variety of conditions that inhibited either nitric oxide synthesis or guanylyl cyclase, and conditions which damaged the endocardial endothelium. Then she looked at the effect of NO on the cholinergic response. This time she found that the heart beat with more force, and that NO from the endocardium endothelium was essential for the effect.
In the last set of experiments, Imbrigno and co-workers looked at the effect of NO on the Frank-Starling response, where an increase in venous filling pressure causes the heart to pump harder. By activating and inhibiting NOS, she found that NO does affect the Frank-Starling response, giving the fish a stronger heart beat in response to physical activity.
So the answer to the question is a resounding YES. NO does modulate fish heart function, in much the same way it does in mammals and amphibians. The difference is that mammals can modulate their heart rate to a much greater extent than fish. Which means that this form of Frank- Starling response regulation is probably more significant to fish than mammals and that NO is definitely the way to a fish's heart.
