title: Role of nitrite in regulation of fetal cephalic circulation in sheep.
abstract: Nitrite has been postulated to provide a reservoir for conversion to nitric oxide (NO), especially in tissues with reduced oxygen levels as in the fetus. Nitrite would thus provide local vasodilatation and restore a balance between oxygen supply and need, a putative mechanism of importance especially in the brain. The current experiments test the hypothesis that exogenous nitrite acts as a vasodilator in the cephalic vasculature of the intact, near term fetal sheep. Fetuses were first instrumented to measure arterial blood pressure and carotid artery blood flow and then studied 4-5 days later while in utero without anaesthesia. Initially l-nitro-arginine (LNNA) was given to block endogenous NO production. Carotid resistance to flow increased 2-fold from 0.54 ± 0.01 (SEM) to 1.20 ± 0.08 mmHg min ml(-1) (in 13 fetuses, P < 0.001), indicating NO tonically reduces cerebral vascular tone. Sodium nitrite (or saline as control) was then infused in increasing step-doses from 0.01 to 33 μm in half-log increments over a period of 2 h. Carotid artery pressure, blood flow and vascular resistance did not change compared to fetuses receiving saline, even at plasma nitrite concentrations two orders of magnitude above the physiological range. The results indicate that while cephalic vascular tone is controlled by endogenous nitric oxide synthase activity, exogenously administered nitrite is not a vasodilator at physiological concentrations in the vasculature served by the carotid artery of fetal sheep.
authors.affiliation: Department of Pediatrics, 11175 Campus Street, 11121 Coleman, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.  ablood@llu.edu.
authors.forename: Giang T
authors.initials: GT
authors.lastname: Truong
authors.forename: Hobe J
authors.initials: HJ
authors.lastname: Schröder
authors.forename: Taiming
authors.initials: T
authors.lastname: Liu
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.forename: Eriko
authors.initials: E
authors.lastname: Kanda
authors.forename: Shannon
authors.initials: S
authors.lastname: Bragg
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000196:embryology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000098:blood supply*; D009573:Nitrites / Q000494:pharmacology*; D011247:Pregnancy; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009573:Nitrites