Maturation of the angiotensin II cardiovascular response in the embryonic White Leghorn chicken (Gallus gallus)

Angiotensin II (Ang II) is an important regulator of cardiovascular function in adult vertebrates. Although its role in regulating the adult system has been extensively investigated, the cardiovascular response to Ang II in embryonic vertebrates is relatively unknown. We investigated the potential of Ang II as a regulator of cardiovascular function in embryonic chickens, which lack central nervous system control of cardiovascular function throughout the majority of incubation. The cardiovascular response to Ang II in embryonic chickens was investigated over the final 50% of their development. Ang II produced a dose-dependent increase in arterial pressure on each day of development studied, and the response increased in intensity as development progressed. The Ang II type-1 receptor nonspecific competitive peptide antagonist [Sar1 ile8] Ang II blocked the cardiovascular response to subsequent injections of Ang II on day 21 only. The embryonic pressure response to Ang II (hypertension only) differed from that of adult chickens, in which initial hypotension is followed by hypertension. The constant level of gene expression for the Ang II receptor, in conjunction with an increasing pressure response to the peptide, suggests that two Ang II receptor subtypes are present during chicken development. Collectively, the data indicate that Ang II plays an important role in the cardiovascular development of chickens; however, its role in maintaining basal function requires further study

Thyroid hormone increases fatty acid use in fetal ovine cardiac myocytes

Abstract Cardiac metabolic substrate preference shifts at parturition from carbohydrates to fatty acids. We hypothesized that thyroid hormone (T3) and palmitic acid (PA) stimulate fetal cardiomyocyte oxidative metabolism capacity. T3 was infused into fetal sheep to a target of 1.5 nM. Dispersed cardiomyocytes were assessed for lipid uptake and droplet formation with BODIPY‐labeled fatty acids. Myocardial expression levels were assessed PCR. Cardiomyocytes from naïve fetuses were exposed to T3 and PA, and oxygen consumption was measured with the Seahorse Bioanalyzer. Cardiomyocytes (130‐day gestational age) exposed to elevated T3 in utero accumulated 42% more long‐chain fatty acid droplets than did cells from vehicle‐infused fetuses. In utero T3 increased myocardial mRNA levels of CD36, CPT1A, CPT1B, LCAD, VLCAD, HADH, IDH, PDK4, and caspase 9. In vitro exposure to T3 increased maximal oxygen consumption rate in cultured cardiomyocytes in the absence of fatty acids, and when PA was provided as an acute (30 min) supply of cellular energy. Longer‐term exposure (24 and 48 h) to PA abrogated increased oxygen consumption rates stimulated by elevated levels of T3 in cultured cardiomyocytes. T3 contributes to metabolic maturation of fetal cardiomyocytes. Prolonged exposure of fetal cardiomyocytes to PA, however, may impair oxidative capacity

Coronary Vascular Growth Matches IGF-1-Stimulated Cardiac Growth in Fetal Sheep

As loss of contractile function in heart disease could often be mitigated by increased cardiomyocyte number, expansion of cardiomyocyte endowment paired with increased vascular supply is a desirable therapeutic goal. Insulin‐like growth factor 1 (IGF‐1) administration increases fetal cardiomyocyte proliferation and heart mass, but how fetal IGF‐1 treatment affects coronary growth and function is unknown. Near‐term fetal sheep underwent surgical instrumentation and were studied from 127 to 134 d gestation (term = 147 d), receiving either IGF‐1 LR3 or vehicle. Coronary growth and function were interrogated using pressure‐flow relationships, an episode of acute hypoxia with progressive blockade of adenosine receptors and nitric oxide synthase, and by modeling the determinants of coronary flow. The main findings were that coronary conductance was preserved on a per‐gram basis following IGF‐1 treatment, adenosine and nitric oxide contributed to hypoxia‐mediated coronary vasodilation similarly in IGF‐1‐treated and Control fetuses, and the relationships between coronary flow and blood oxygen contents were similar between groups. We conclude that IGF‐1‐stimulated fetal myocardial growth is accompanied by appropriate expansion and function of the coronary vasculature. These findings support IGF‐1 as a potential strategy to increase cardiac myocyte and coronary vascular endowment at birth