Red-blood-cell augmentation of hypoxic pulmonary vasoconstriction: hematocrit dependence and the importance of nitric oxide.
Red blood cells (RBCs) are known to augment hypoxic pulmonary vasoconstriction (HPV). To determine whether this phenomenon is hematocrit (Hct) dependent and related to alterations of either nitric oxide (NO) or adenosine metabolism, we studied mechanically ventilated, pump-perfused lungs from euthanized New Zealand White rabbits. Lungs were perfused in situ in a recirculating manner at constant flow; perfusates consisted of Krebs-Henseleit buffer or buffer plus washed RBCs at a Hct of 10% or 30%. HPV was quantitated as the increase in pulmonary artery pressure (Ppa) from baseline after 5 min of hypoxia. In three experimental sets, we studied the effects of Hct on HPV and expired NO, the effects of nitric oxide synthase (NOS) inhibition, and the effects of adenosine receptor blockade. HPV was greater at a higher Hct, and expired NO varied inversely with Hct and decreased with hypoxia. NOS inhibition eliminated RBC-dependence of HPV. Adenosine-receptor blockade did not affect the RBC-dependence of HPV. We conclude that HPV is dependent on Hct, and that this phenomenon may be related to scavenging of NO but not adenosine by RBCs.
Deem
S
S
Department of Anesthesiology, Puget Sound Veterans Affairs Health System and the University of Washington, Seattle 98195-6540, USA. sdeem@u.washington.edu
Swenson
E R
ER
Alberts
M K
MK
Hedges
R G
RG
Bishop
M J
MJ
D000241:Adenosine / Q000502:physiology; D000818:Animals; D004912:Erythrocytes / Q000502:physiology*; D006400:Hematocrit; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D014661:Vasoconstriction / Q000502:physiology*
D058915:Purinergic P1 Receptor Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine