Endothelial modulation of pH-dependent pressor response in isolated perfused rabbit lungs.
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the increase in Ppa caused by hypercapnia is modulated by EDRF, and 3) the pulmonary EDRF genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis.
Yamaguchi
K
K
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Takasugi
T
T
Fujita
H
H
Mori
M
M
Oyamada
Y
Y
Suzuki
K
K
Miyata
A
A
Aoki
T
T
Suzuki
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D016857:Hypocapnia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011652:Pulmonary Circulation / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D010208:Papaverine