Hif‐1α is not required for the development of cardiac adrenergic control in zebrafish (Danio rerio). Issue 7 (19th July 2021)

• Record Type: Journal Article
• Authors: Joyce, William; Perry, Steve F.
• Is Part Of: Journal of experimental zoology. Volume 335:Issue 7(2021)
• Page Start: 623
• Page End: 631
• Publication Date: 2021-07-19
• Subjects: adrenaline -- heart rate -- hypoxia‐inducible factor -- innervation -- tyrosine hydroxylase; Zoology -- Periodicals; Zoology; Animal Population Groups -- physiology; Zoology; Electronic journals; Periodical; Periodicals; 590
• DOI: 10.1002/jez.2507
• Languages: English
• ISSNs: 2471-5646

Abstract

Abstract: Adrenergic regulation, acting via the sympathetic nervous system, provides a major mechanism to control cardiac function. It has recently been shown that hypoxia inducible factor‐1α (Hif‐1α) is necessary for normal development of sympathetic innervation and control of cardiac function in the mouse. To investigate whether this may represent a fundamental trait shared across vertebrates, we assessed adrenergic regulation of the heart in wild‐type and Hif‐1α knockout ( hif‐1α −/− ) zebrafish ( Danio rerio ). Wild‐type and hif‐1α −/− zebrafish larvae (aged 4 and 7 days postfertilisation) exhibited similar routine heart rates within a given age group, and β‐adrenergic receptor blockade with propranolol universally reduced heart rate to comparable levels, indicating similar adrenergic tone in both genotypes. In adult fish, in vivo heart rate measured during anaesthesia was identical between genotypes. Treatment of spontaneously beating hearts in vitro with adrenaline revealed a similar positive chronotropic effect and similar maximum heart rates in both genotypes. Tyrosine hydroxylase immunohistochemistry with confocal microscopy demonstrated that the bulbus arteriosus (outflow tract of the teleost heart) of adult fish was particularly well innervated by sympathetic nerves, and nerve density (as a percentage of bulbus arteriosus area) was similar between wild‐types and hif‐1α −/− mutants. In summary, we did not find any evidence that adrenergic cardiac control was perturbed in larval or adult zebrafish lacking Hif‐1α. We conclude that Hif‐1α is not essential for the normal development of cardiovascular control or adult sympathetic cardiac innervation in zebrafish, although it is possible that it plays a redundant or auxiliary role. Abstract : Hypoxia inducible factor‐1α (Hif‐1α) has recently been implicated in the development of cardiac innervation in mammals. By contrast, we report that adrenergic control of the heart in Hif‐1α knockout zebrafish is similar to that in wild‐type, indicating that Hif‐1α may not be strictly necessary for normal cardiac innervation. Research Highlights: Hypoxia inducible factor‐1α (Hif‐1α) is involved in the development of cardiac innervation in mammals. By contrast, cardiac adrenergic control in Hif‐1α knockout zebrafish is similar to wild‐type, indicating that Hif‐1α is nonessential.