Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep

Abstract

This study examined the hypothesis that the development of hydrops fetalis after asphyxia in the 0.6 gestation sheep fetus would be associated with activation of the fetal renin-angiotensin system (RAS). Fetuses were randomly assigned to either sham occlusion (n = 7) or to 30 min of asphyxia induced by complete umbilical cord occlusion for 30 min (n = 8). Asphyxia led to severe bradycardia and hypotension that resolved after release of occlusion. After occlusion, plasma renin concentration was significantly increased in the asphyxia group compared with controls (P < 0.005) after 3 min (16.3 +/- 5.3 vs. 4.1 +/- 1.3 ng. ml(-1). h(-1)), and 72 h (30.6 +/- 6.3 vs. 3.7 +/- 1.2 ng. ml(-1). h(-1)). Renal renin concentrations and mRNA levels were significantly greater in the asphyxia group after 72 h of recovery. All fetuses in the asphyxia group showed generalized tissue edema, ascites, and pleural effusions after 72 h of recovery. In conclusion, asphyxia in the preterm fetus caused sustained activation of the RAS, which was associated with hydrops fetalis.

Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm fetal sheep

“…Alternatively, fetal hypoxia is associated with altered eNOS-dependent relaxation of umbilical vessels, with increased eNOS expression in umbilical arteries and reduced eNOS in the umbilical veins (Hracsko, et al, 2009), regulated at least in part by greater arginase-2 production in the umbilical venous circulation, reducing eNOS activity (Krause, et al, 2013). Further studies are needed to assess whether JI-10 could modulate these differential responses to hypoxia to alter the net hydrostatic pressure difference across the placenta and so promote fetal fluid accumulation (Lumbers, et al, 2001). …”

The role of the sympathetic nervous system in postasphyxial intestinal hypoperfusion in the pre‐term sheep fetus

“…Although it was not possible to evaluate myocardial histology and function directly in the present study, there is considerable clinical and experimental evidence to show that reversible myocardial injury and associated cardiac dysfunction are common during recovery from exposure to perinatal asphyxia (Gunn et al 2000; Lumbers et al 2001; Hunt & Osborn, 2002). Consistent with the hypothesis of early myocardial dysfunction, in the present study phentolamine infusion led to a reduction in blood pressure for 3–4 h despite normalization of SMA blood flow for most of this period.…”

Cortisol and ACTH responses to severe asphyxia in preterm fetal sheep

“…In contrast, and consistent with previous studies of the renal responses to asphyxia at this gestational age (Quaedackers et al 2004 b ), we found marked initial hypertension during complete umbilical cord occlusion associated with an initial, actively mediated fall in FBF, as shown by the very rapid and large increase in vascular resistance in the first 6 min after the start of umbilical cord occlusion. In the near‐term fetus the initial vasoconstriction during asphyxia is primarily mediated by sympathetic neural activity (Jensen & Lang, 1992) and possibly augmented by release of stress hormones such as arginine vasopressin and renin–angiotensin system (RAS) activation (Raff et al 1991; Giussani et al 1994 b ; Rosnes et al 1998); limited data suggest that this also occurs in preterm fetuses (Cheung, 1992; Lumbers et al 2001). Finally, the rise in circulating cortisol demonstrated in the present study may also help to support initial hypertension, as discussed below.…”