Fetal and adult cerebral artery K(ATP) and K(Ca) channel responses to long-term hypoxia.
High-altitude long-term hypoxia (LTH) alters cerebral vascular contractile and relaxation responses in both fetus and adult. We tested the hypotheses that LTH-mediated vascular responses were secondary to altered K+ channel function and that in the fetus these responses differ from those of the adult. In middle cerebral arteries (MCA) from both nonpregnant adult and fetal (approximately 140 days gestation) sheep, which were either acclimatized to high altitude (3,820 m) or sea-level controls, we measured norepinephrine (NE)-induced contractions and intracellular Ca2+ concentration ([Ca2+]i) simultaneously, in the presence or absence of different K+ channel openers or blockers. In adult MCA, LTH was associated with approximately 20% decrease in NE-induced tension and [Ca2+]i, with a significant increase in Ca2+ sensitivity. In contrast, in fetal MCA, LTH failed to affect significantly NE-induced contraction or [Ca2+]i but significantly decreased the ATP-sensitive K+ (K(ATP)) channel and Ca2+-activated K+ (K(Ca)) channel-mediated relaxation. The significant effect of K(ATP) and K(Ca) channel activators on the relaxation responses and the fact that K+ channels play a key role in myogenic tone support the hypotheses that K+ channels play an important role in hypoxia-mediated responses. These results also support the hypothesis of significant developmental differences with maturation from fetus to adult.
Long
Wen
W
Center for Perinatal Biology, Department of Physiology, Loma Linda University, School of Medicine, Loma Linda, California 92350, USA. llongo@som.llu.edu
Zhang
Lubo
L
Longo
Lawrence D
LD
D000064:Acclimatization / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000531:Altitude; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000196:embryology* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011247:Pregnancy; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine