Cardiovascular and respiratory developmental plasticity under oxygen depleted environment and in genetically hypoxic...

Known vertebrate response to low oxygen concentration include change in carbohydrate metabolism, increase in nitric oxide, stimulation of red blood cell and hemoglobin production and induction of gene expression for glycolytic enzymes and hormones. Also, extreme hypoxia plays main role in pathological studies of cardiac dysfunction. The morphological and physiological developmental studies of the cardiovascular system under low oxygen are important as it is directly related to oxygen supply and consumption. Furthermore, cardiac function demands high energy during system development and thus it is most likely to be affected by hypoxia. Zebrafish (Danio rerio) can act as a model organism for oxygen demand management study as in natural environment, due to ecological disturbances, it is exposed to changes in oxygen concentrations routinely and thus would have natural ability to cope with it for survival. We have studied, in zebrafish, i) cardiovascular flexibility under extreme hypoxia (PO(2)=20 Torr, 3 kPa) at 3-10 dpf (days post-fertilization), ii) cardiac re-animation in normoxia (PO(2)=152 Torr, 20 kPa) after 90 min of anoxia (PO(2)=0 Torr, 0 kPa)-induced suspended animation at 4 dpf and iii) oxygen consumption in 8 dpf von Hippel-Lindau (vhl(-)(/)(-)) mutant that exhibits an artificial hypoxic response under normoxic conditions. In hypoxic fish, cardiac output, stroke volume and end-diastolic volume were elevated while intersegmental blood vessels vascularization index at 6 dpf and at 10 dpf was 22% and 11% higher respectively as compared to the normoxic fish. The heart rate in hypoxic fish was lower until 6 dpf and then showed an elevated trend. There was no significant difference in body length between the hypoxic and normoxic individuals. The observed changes may have enhanced the performance of the cardiovascular system for oxygen uptake. We also report for the first time that the post-anoxia re-animated heart rate returns to normal after 48h. Measurement of oxygen consumption in 8 dpf hyperventilating vhl(-)(/)(-) mutant was, unexpectedly, significantly lower than the non-mutant fish of the same age which point towards artificial hypoxic signal from brain in these mutants.