No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in pigs.
OBJECTIVE
In the severely ill intensive care patients metabolic acidosis and hypoxia often co-exist. We studied the effects of metabolic acidosis on nitric oxide synthase (NOS) dependent and NOS independent nitric oxide (NO) production in hypoxic and hyperoxic lung (HL) regions in a pig model.


METHODS
Eighteen healthy anaesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Six pigs received HCl infusion (HCl group), six pigs received the non-specific NOS inhibitor N(ω) -nitro-l-arginine methyl ester (l-NAME) and HCl infusions (l-NAME + HCl group) and six pigs received buffered Ringer's solution (control group). NO concentration in exhaled air (ENO), NOS activity in lung tissue, and regional pulmonary blood flow were measured.


RESULTS
Metabolic acidosis, induced by infusion of HCl, decreased the relative perfusion to the hypoxic LLL from 7 (3) [mean (SD)] to 3 (1) % in the HCl group (P < 0.01), and from 4 (1) to 1 (1) % in the l-NAME + HCl group (P < 0.05), without any measurable significant changes in ENO from hypoxic or HL regions There were no significant differences between the HCl and control groups for Ca(2+) -dependent (cNOS) or Ca(2+) -independent NOS (iNOS) activity in hypoxic or HL regions.


CONCLUSIONS
Metabolic acidosis augmented the hypoxic pulmonary vasoconstriction, without any changes in pulmonary NOS dependent or NOS independent NO production. When acidosis was induced during ongoing NOS blockade, the perfusion of hypoxic lung regions was almost abolished, indicating acidosis-induced pulmonary vasoconstriction was not NO dependent.
Department of Anaesthesiology and Intensive Care, University Hospital, Uppsala, Sweden. manja.nilsson@akademiska.se
M C A
MC
Nilsson
F
F
Fredén
P
P
Wiklund
K
K
Hambraeus-Jonzon
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D034421:Sus scrofa
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester