Journal of Applied Physiology
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J Appl Physiol 92: 1692-1701, 2002; doi:10.1152/japplphysiol.01110.2001
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Vol. 92, Issue 4, 1692-1701, April 2002

Fetal and adult cerebral artery KATP and KCa channel responses to long-term hypoxia

Wen Long, Lubo Zhang, and Lawrence D. Longo

Center for Perinatal Biology, Departments of Physiology, Pharmacology, and Obstetrics and Gynecology, Loma Linda University, School of Medicine, Loma Linda, California 92350

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 (~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 ~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+ (KATP) channel and Ca2+-activated K+ (KCa) channel-mediated relaxation. The significant effect of KATP and KCa 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.

acclimatization; high altitude; cerebral circulation; vascular smooth muscle; norepinephrine; potassium channels; fetus


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