title: Chronic hypoxia increases the NO contribution of acetylcholine vasodilation of the fetal guinea pig heart.
abstract: To investigate the effect of chronic hypoxia (HPX) on vasodilation of the fetal heart, we exposed pregnant guinea pigs to room air or 12% O(2) for 4, 7, or 10 days. We excised hearts from anesthetized fetuses (60 +/- 3 days; 65-day gestation = term) and measured changes in both the coronary artery pressure of the isolated constant-flow preparation and endothelial nitric oxide synthase (eNOS) mRNA of fetal ventricles. Dilator responses to cumulative addition (10(-9)-10(-5) M) of acetylcholine and sodium nitroprusside in prostaglandin F(2alpha) (5 x 10(-6) M)-constricted hearts were similar among normoxia (NMX), 4-, 7-, and 10-day HPX (control). Nitro-L-arginine (L-NA, 10(-4)M), a NOS inhibitor, inhibited maximal acetylcholine dilation of hearts exposed to 10-day HPX greater than NMX, 4-, and 7-day HPX. Hypoxia (after 7 and 10 days) increased eNOS mRNA of fetal ventricles compared with NMX and 4-day HPX. 4-Aminopyridine (3 mM), a voltage-dependent K(+)-channel inhibitor, inhibited acetylcholine- but not sodium nitroprusside-induced dilation of NMX and 10-day HPX hearts to a similar magnitude. Glibenclamide (10(-5) M), an ATP-sensitive K(+)-channel inhibitor, had no effect on vasodilation. We conclude that chronic HPX increases the contribution of NO but does not alter K(+)-channel activation in response to acetylcholine-stimulated coronary dilation. Thus increases in NO production via upregulation of eNOS gene expression may be an adaptive response to chronic HPX in the fetal coronary circulation.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21158, USA.
authors.forename: L P
authors.initials: LP
authors.lastname: Thompson
authors.forename: K
authors.initials: K
authors.lastname: Aguan
authors.forename: G
authors.initials: G
authors.lastname: Pinkas
authors.forename: C P
authors.initials: CP
authors.lastname: Weiner
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000196:embryology* / Q000503:physiopathology; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000196:embryology / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage; D026902:Potassium Channel Blockers; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D009599:Nitroprusside; D009569:Nitric Oxide; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D010100:Oxygen; D005905:Glyburide