Yonsei Med J.  1998 Jun;39(3):261-267. 10.3349/ymj.1998.39.3.261.

Effects of hypoxia on pulmonary vascular contractility

• Lee YH
• Seo JH
• Kang BS

• KMID: 711556
• DOI: http://doi.org/10.3349/ymj.1998.39.3.261

Abstract

Although hypoxic pulmonary vasoconstriction (HPV) has been recognized by many researchers, the precise mechanism remains unknown. As isolated pulmonary arteries will constrict in vitro in the response to hypoxia, the oxygen sensor/transduction mechanism must reside in the pulmonary arterial smooth muscle or in the endothelium, or in both. Unfortunately, much of the current evidence is conflicting, especially as to the dependency of HPV on the endothelium and the role of a K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPV on the endothelium and the role of a K+ channel on HPV in rat pulmonary artery. The effects of hypoxia were investigated in isolated main pulmonary arteries precontracted with norepinephrine. Vascular rings were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and this was maintained for 20 min. Hypoxia elicited a vasoconstriction in arteries with endothelium. Mechanical disruption of the endothelium abolished HPV. There was no difference between the amplitude of the HPV induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on a subsequent response to hypoxia. Inhibition of NO synthesis by treatment with N(omega)-nitro-L-arginine reduced HPV, but inhibition of a cyclooxygenase pathway by treatment with indomethacin had no effect on HPV. Blockades of a tetraetylammonium chloride-sensitive K+ channel abolished HPV. Verapamil, a Ca2+ entry blocker reduced HPV. In conclusion, these results suggest that HPV was dependent on the endothelium and that HPV can be considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation such as the opening of a K+ channels.

Keyword

Hypoxic pulmonary vasoconstriction; nitric oxide; K+ channel

MeSH Terms

Animal
Anoxia/physiopathology*
Blood Vessels/physiopathology
Calcium Channel Blockers/pharmacology
Cyclooxygenase Inhibitors/pharmacology
Enzyme Inhibitors/pharmacology
Indomethacin/pharmacology
Nitroarginine/pharmacology
Pulmonary Circulation/physiology*
Pulmonary Circulation/drug effects
Rats
Tetraethylammonium/pharmacology
Vasoconstriction/physiology*
Vasoconstriction/drug effects
Verapamil/pharmacology