title: Enhanced nitric oxide activity offsets peripheral vasoconstriction during acute hypoxaemia via chemoreflex and adrenomedullary actions in the sheep fetus.
abstract: We tested the hypothesis that enhanced nitric oxide (NO) opposes fetal peripheral vasoconstrictor responses to acute hypoxaemia via actions involving the carotid chemoreflex and the adrenal medulla. The hypothesis was tested in the late gestation ovine fetus using a novel NO clamp technique, which involves fetal combined treatment with the NO synthase inhibitor, L-NAME, and the NO donor, sodium nitroprusside. In contrast to treatment with L-NAME alone, combined fetal treatment with L-NAME and nitroprusside prevents generalized vasoconstriction and pronounced hypertension, not only maintaining basal cardiovascular function, but also permitting blockade of the de novo synthesis of NO during hypoxaemia while compensating for the tonic production of the gas. Under general anaesthesia, seven sheep fetuses were surgically prepared with catheters and a femoral Transonic flow probe. Five days after surgery, fetuses were subjected to a 3 h protocol: 1 h normoxia, 1 h hypoxaemia and 1 h recovery. Fetal hypoxaemia was induced during either fetal infusion with saline or treatment with the NO clamp. During saline infusion, fetuses responded to hypoxaemia with transient bradycardia, femoral vasoconstriction and increases in plasma noradrenaline and adrenaline. During fetal treatment with the NO clamp, bradycardia persisted and there were greater peripheral vasoconstrictor and catecholaminergic responses to hypoxaemia. Further analysis showed that NO clamp treatment enhanced the chemoreflex component of the fetal cardiovascular defence to acute hypoxaemia. These data support the hypothesis that enhanced NO synthesis during acute hypoxaemia offsets fetal peripheral vasoconstrictor responses to hypoxaemia via chemoreflex and adrenomedullary actions.
authors.affiliation: Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Morrison
authors.forename: David S
authors.initials: DS
authors.lastname: Gardner
authors.forename: Andrew J W
authors.initials: AJ
authors.lastname: Fletcher
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Bloomfield
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000208:Acute Disease; D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D002628:Chemoreceptor Cells / Q000502:physiology; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000502:physiology*; D005865:Gestational Age; D006339:Heart Rate / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D012018:Reflex / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012756:Sheep; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D002395:Catecholamines; D009569:Nitric Oxide; D010100:Oxygen