title: Role of nitric oxide in the cerebral circulation during hypotension after hemorrhage, ganglionic blockade and diazoxide in awake goats.
abstract: The role of nitric oxide in cerebrovascular response to hypotension was analyzed by evaluating the changes in cerebrovascular resistance after inhibition of nitric oxide synthesis with Nw-nitro-L-arginine methyl ester (L-NAME) during three types of hypotension in conscious goats. Blood flow to one brain hemisphere was electromagnetically measured, hypotension was induced by controlled bleeding, and by i.v. administration of hexametonium (ganglionic blocker) or of diazoxide (vasodilator drug), and L-NAME was injected by i.v. route (35 mg kg-1). Under control conditions (13 goats), L-NAME increased arterial pressure from 98 +/- 3 to 123 +/- 4 mmHg and decreased cerebral blood flow from 65 +/- 3 to 40 +/- 3 ml min-1 (all P < 0.001); cerebrovascular resistance increased from 1.52 +/- 0.04 to 3.09 +/- 0.013 mmHg ml-1 min-1 (P < 0.01) (delta = 1.59 +/- 0.12 mmHg ml-1 min-1). After bleeding (five goats), mean arterial pressure decreased to 60 +/- 4 mmHg and cerebral blood flow decreased to 37 +/- 4 ml min-1 (all P < 0.01); cerebrovascular resistance did not change (1.56 +/- 0.14 vs. 1.54 +/- 0.12 mmHg ml-1 min-1, P > 0.05). During this hypotension, L-NAME increased arterial pressure to reach the normotensive values an did not affect the hypotensive values for cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 2.91 +/- 0.19 mmHg ml-1 min-1 (P < 0.01) (delta = 1.37 +/- 0.16 mmHg ml-1 min-1), and this increment is comparable to that under control conditions (P > 0.05). Ganglionic blockade (six goats) decreased arterial pressure to 67 +/- 2 mmHg) and did not affect significantly cerebral blood flow; cerebrovascular resistance decreased from 1.71 +/- 0.11 to 1.05 +/- 0.09 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 103 +/- 6 mmHg (P < 0.001), and did not affect cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 1.68 +/- 0.18 mmHg ml-1 min-1 (P < 0.01) (delta = 0.63 +/- 0.10 mmHg ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Diazoxide (six goats) decreased arterial pressure to 69 +/- 5 mmHg (P < 0.01) without changing cerebral blood flow; cerebrovascular resistance decreased from 1.89 +/- 0.11 to 1.16 +/- 0.14 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 87 +/- 6 mmHg (P < 0.05) and did not affect the hypotensive values for cerebral blood flow (P > 0.05); cerebrovascular resistance increased from the hypotensive values to 1.53 +/- 0.13 mmHg ml-1 min-1 (P < 0.05) (delta = 0.36 +/- 0.06 mmHg-1 ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Therefore, the role of nitric oxide in cerebrovascular response to hypotension may differ in each type of hypotension, as this role during hemorrhagic hypotension may not change and during hypotension by ganglionic blockade or diazoxide may decrease. These differences may be related to changes in nitric oxide release as stimuli on the endothelium (shear stress and sympathetic activity) may vary in each type of hypotension.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain. godofredo.dieguez@uam.es
authors.forename: G
authors.initials: G
authors.lastname: Diéguez
authors.forename: N
authors.initials: N
authors.lastname: Fernández
authors.forename: M A
authors.initials: MA
authors.lastname: Sánchez
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.forename: A L
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: L
authors.initials: L
authors.lastname: Monge
authors.forename: B
authors.initials: B
authors.lastname: Gómez
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003981:Diazoxide; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005730:Ganglionic Blockers; D006041:Goats; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage; D018738:Hexamethonium; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents
chemical_list: D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D018738:Hexamethonium; D003981:Diazoxide; D019331:NG-Nitroarginine Methyl Ester