Cardiac influence of the β3-adrenoceptor in the goldfish (Carassius auratus): a protective role under hypoxia?

Abstract

The goldfish (Carassius auratus) exhibits a remarkable capacity to survive and remain active under prolonged and severe hypoxia, representing a well-suited model to study cardiac function when oxygen availability represents a limiting factor. Under hypoxia, the goldfish heart increases its performance, this representing a putative component of hypoxia tolerance; however, underlying mechanisms have not been yet elucidated. We aimed to investigate the role of β3-ARs in the mechanisms which modulate the goldfish heart performance, also in relation to oxygen levels. By western blotting analysis, we found that the goldfish heart expresses β3-ARs, and this expression increases under hypoxia. Effects of β3-ARs stimulation were analysed by using an ex vivo working heart preparation. Under normoxia, the β3-ARs selective agonist BRL37344 (10−12-10−7M) elicited a concentration-dependent increase of contractility abolished by the specific β3-AR antagonist (SR59230A; 10−8M), but not by α/β1/β2-ARs inhibitors (phentolamine, nadolol, and ICI118,551; 10−7M). Under acute hypoxia, BRL37344 did not affect the goldfish heart performance. However, SR59230A, but not phentolamine, nadolol, and ICI118,551, abolished the time-dependent enhancement of contractility which characterizes the hypoxic goldfish heart. Under both normoxia and hypoxia, adenylate cyclase and cAMP were found to be involved in the β3-ARs-dependent downstream transduction pathway. Our findings suggest the presence of functional β3-ARs in the goldfish heart, whose activation modulates the basal performance and contributes to the hypoxia-dependent increase of contractility.