Chronic hypoxia inhibits contraction of fetal arteries by increased endothelium-derived nitric oxide and prostaglandin synthesis.
OBJECTIVE
Chronic hypoxia causes redistribution of fetal cardiac output by mechanisms poorly understood. We tested the hypothesis that chronic hypoxia alters vascular reactivity of arteries from near-term fetal guinea pigs.


METHODS
Pregnant guinea pigs (50 days, term = 65 days) were exposed to either normoxia (room air) or hypoxia (12% O2) for 14 days. Carotid artery ring segments from anesthetized fetuses were mounted onto myographs for measurement of force. Contractile responses to cumulative addition of prostaglandin F2alpha (PGF2alpha, 10(-9) M to 10(-5) M), U46619, a thromboxane mimetic (10(-12) M to 12(-6) M), and KCl (10 to 120 mM) were measured in the presence and absence of INDO (INDO, 10(-5) M) alone and INDO plus nitro-L-arginine (LNA, 10(-4) M), or INDO plus N6-iminoethyl-L-lysine (LNIL, 5 x 10(-5) M, a selective iNOS inhibitor), and measured in endothelium-intact and denuded arteries. Nitric oxide synthase (NOS) activity was measured in isolated arteries by 14C-L-arginine to 14C-L-citrulline conversion.


RESULTS
Hypoxia decreased contractile responses to both PGF2alpha and U46619 under control conditions. Maximal contraction to both agonists was increased in hypoxemic arteries after INDO alone and INDO + LNA compared to normoxic controls. Endothelium-denudation abolished the differences between the groups. KCl contraction was unaffected by hypoxia. LNIL potentiated maximal PGF(2alpha) contraction but was similar between groups. Hypoxia increased (P < .05) total and Ca(2+)-dependent NOS activities by 1.7- and 2.1-fold, respectively, but had no effect on Ca(2+)-independent activity.


CONCLUSIONS
Chronic hypoxia alters vascular reactivity of fetal carotid arteries by increasing the contribution of both vasodilator prostaglandins and nitric oxide and suggests that changes in local vascular mechanisms may be altered by chronic hypoxia.
Thompson
Loren P
LP
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. lthompson1@umm.edu
Aguan
Kripamoy
K
Zhou
Hui
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000196:embryology* / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D002339:Carotid Arteries / Q000196:embryology / Q000503:physiopathology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D020567:Fetal Weight; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000196:embryology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D002118:Calcium