cyclic-gmp and Acidosis--Respiratory

Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs.. Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO(2)) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured.. There were no differences between the groups for ENO, Ca(2+)-independent or Ca(2+)-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q (LLL)/Q (T)) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q (LLL)/Q (T) increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q (LLL)/Q (T) remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO(2) (p < 0.01)(.). Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.

Topics: Acidosis, Respiratory; Animals; Blood Gas Analysis; Carbon Dioxide; Cyclic GMP; Exhalation; Hypercapnia; Hyperoxia; Nitric Oxide; Pulmonary Artery; Regional Blood Flow; Respiration, Artificial; Swine; Vasoconstriction

We determined whether inhaling low levels of nitric oxide (NO) gas could selectively reverse hypoxic pulmonary vasoconstriction in the near-term newborn lamb and whether vasodilation would be attenuated by respiratory acidosis. To examine the mechanism of air and NO-induced pulmonary vasodilation soon after birth, we measured plasma and lung cGMP levels in the newly ventilated fetal lamb. Breathing at FIO2 0.10 nearly doubled the pulmonary vascular resistance index in newborn lambs and decreased pulmonary blood flow primarily by reducing left-to-right blood flow through the ductus arteriosus. Inhaling 20 ppm NO at FIO2 0.10 completely reversed hypoxic pulmonary vasoconstriction within minutes. Maximum pulmonary vasodilation occurred during inhalation of > or = 80 ppm NO. Breathing 8% CO2 at FIO2 0.10 elevated the pulmonary vascular resistance index to a level similar to breathing at FIO2 0.10 without added CO2. Respiratory acidosis did not attenuate pulmonary vasodilation by inhaled NO. In none of our studies did inhaling NO produce systemic hypotension or elevate methemoglobin levels. Four minutes after initiating ventilation with air in the fetal lamb lung, cGMP concentration nearly doubled without changing preductal plasma cGMP concentration. Ventilation with 80 ppm NO at FIO2 0.21 increased both lung and preductal plasma cGMP concentration threefold. Our data suggest that inhaled NO gas is a rapid and potent selective vasodilator of the newborn pulmonary circulation with an elevated vascular tone due to hypoxia and respiratory acidosis that acts by increasing lung cGMP concentration.

Topics: Acidosis, Respiratory; Administration, Inhalation; Animals; Animals, Newborn; Cyclic GMP; Hemodynamics; Hypoxia; Models, Biological; Nitric Oxide; Pulmonary Artery; Pulmonary Circulation; Sheep; Vascular Resistance; Vasoconstriction