Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density
Open Access
- 6 January 2009
- journal article
- Published by Springer Science and Business Media LLC in BMC Cardiovascular Disorders
- Vol. 9 (1), 1
- https://doi.org/10.1186/1471-2261-9-1
Abstract
Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury, yet the effects on normal cardiac mechanical performance are poorly understood. Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen) for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05). Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P < 0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance.Keywords
This publication has 60 references indexed in Scilit:
- Cold acclimation induces physiological cardiac hypertrophy and increases assimilation of triacylglycerol metabolism through lipoprotein lipaseBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2008
- Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathyAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Contribution of α2‐adrenoceptors and Y1 neuropeptide Y receptors to the blunting of sympathetic vasoconstriction induced by systemic hypoxia in the ratJournal Of Physiology-London, 2007
- Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heartCardiovascular Research, 2005
- Acute Effects of Nonlethal in utero Hypoxia on Fetal Guinea Pig Heart and Lack of Persistent Cardiac or Cerebral Effects in the NeonateNeonatology, 2004
- Effect of fetal hypoxia on heart susceptibility to ischemia and reperfusion injury in the adult ratJournal of the Society for Gynecologic Investigation, 2003
- Investigation of mechanisms that mediate reactive hyperaemia in guinea‐pig hearts: role of KATP channels, adenosine, nitric oxide and prostaglandinsBritish Journal of Pharmacology, 2001
- Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1αGenes & Development, 1998
- Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation.JCI Insight, 1997
- The influence of endothelium-derived nitric oxide on myocardial contractile functionInternational Journal of Cardiology, 1995