Fetal cardiac and cerebrovascular acclimatization responses to high altitude, long-term hypoxia.
In response to high altitude long-term hypoxemia, the heart of fetal sheep shows a decrease in cardiac output that is secondary to a decrease in myocardial cell contractile function. The intracellular mechanisms responsible for these reductions might include reduced myofibrillar Mg(2+)-activated ATPase. There is also a decrease in beta(1)-adrenergic receptor stimulated augmentation of myocardial contraction. An overproduction of cAMP by beta(1)-adrenergic receptor stimulation, resulting in overphosphorylation of troponin I, may reduce calcium binding by troponin C. Fetal coronary arteries have a reduced contractile response to K(+) depolarization and a reduced sensitivity to a thromboxane A(2) receptor agonist-stimulated contraction. Cerebral arteries of adult sheep (but not the fetus) show decreased responses to both K(+)-depolarization and norepinephrine-induced contraction. Nonetheless, cerebral arteries in the long-term hypoxic fetus demonstrated a number of significant changes from control. For the cerebral arteries in general, high altitude hypoxia is associated with augmented or upregulation of presynaptic functions. In contrast, postsynaptic functions tend to be significantly depressed or downregulated. The results emphasize the role of high altitude, long-term hypoxemia in modulating adrenergic- and serotonergic-mediated signal transduction in the cerebral vasculature. They specifically highlight the significant differences in acclimatization responses between the fetus and adult.
Gilbert
Raymond D
RD
Departments of Physiology and Pharmacology, Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA, USA. rgilbert@som.llu.edu
Pearce
William J
WJ
Longo
Lawrence D
LD
D000064:Acclimatization / Q000502:physiology*; D000531:Altitude; D002320:Cardiovascular Physiological Phenomena; D002536:Cerebral Arteries / Q000196:embryology / Q000294:innervation / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000196:embryology*; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000502:physiology; D013995:Time; D014655:Vascular Resistance / Q000502:physiology