Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction.
The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured.


RESULTS
In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP.


CONCLUSIONS
The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.
Heller
A
A
Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. heller-a@rcs.urz.tu-dresden.de
Ragaller
M
M
Schmeck
J
J
Flüth
H
H
Müller
M
M
Albrecht
D M
DM
Koch
T
T
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D009569:Nitric Oxide; C086539:BQ 788; D001120:Arginine; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester