Korean J Anesthesiol.  1995 Nov;29(5):604-612. 10.4097/kjae.1995.29.5.604.

Mechanism of Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Pulmonary Artery

Affiliations
  • 1Department of Anesthesiology, School of Medicine, Hanyang University, Seoul, Korea.

Abstract

Hypoxic pulmonary vasoconstriction(HPV) plays an important role in matching ventilation and perfusion, and in a homeostatic compensatory mechanism for maintaining arterial blood oxygen tension. The purpose of this study was to explore effect of hypoxia on the vascular tension and to elucidate mechanism underlying hypoxic pulmonary vasoconstriction. The ring segments of the pulmonary artery were taken from forty rabbits(2~2.5 kg, male). Each ring was attached to an isometric force transducer(Grass FT-03) and suspended in a tissue bath(37degrees C) filled with 5 ml Krebs solution, aerated with 95% O2 + 5% CO2(pH 7.4) gas mixture. During 90 minutes of equilibrium period, the Krebs solution was changed every 15 minutes and the last resting tension was adjusted to 2 gm. After precontraction of the preparations with K(+) 40 mM, the aerating gas mixture was replaced by hypoxic gas(95% N2 + 5% CO2) and changes in vascular tension of isolated pulmonary artery with(n=36) and without endothelium(n=14) were recorded for 60 minutes. HPV induced biphasic vasoactive effects. To determine the mechanism of the vasorelaxing response, the pulmonary arterial rings were pretreated with indomethacin(n=8), L-nitro(w) arginine methyl ester(L-NAME, n=l0), tetra ethyl ammonium(TEA, n=12), glybenclamide(n=l1). And also to elucidate the mechanism of the hypoxic vasoconstricting response, effects of Ca free solution and pretreatment of ryanodine on the HPV were examined. The results obtained were as follows: 1) Transient phase 1 contraction followed by long lasting(about 30 minutes) relaxation and sustained phase 2 contraction were induced by hypoxic gas(95% N2+5% CO2) in rabbit pulmonary artery. 2) In endothelium removed pulmonary artery, transient phase 1 contraction was not apparent. 3) Vasorelaxation was partially blocked by K' channel blockers(TEA, glybenclamide). 4) Indomethacin and L-NAME pretreatments did not affect on the vasorelaxing response of the HPV to hypoxia. 5) Sustained phase 2 contraction was blocked by calcium free Krebs solution. 6) Indomethacin and ryanodine pretreatments did not change the phase 1 and phase 2 vasocontsricting reponses. The results of present study suggest that hypoxia-induced phase 1 contractile response is endothelium dependent, while phase 2 contractile response is dependent on calcium influx, and that the vasorelaxant response is partially mediated by K(+) channel.

Keyword

Hypoxic pulmonary vasoconstriction; Vasodilation; EDCF; Endothelin

MeSH Terms

Anoxia
Arginine
Calcium
Characidae
Endothelins
Endothelium
Indomethacin
NG-Nitroarginine Methyl Ester
Oxygen
Perfusion
Pulmonary Artery*
Relaxation
Ryanodine
Vasoconstriction*
Vasodilation
Ventilation
Arginine
Calcium
Endothelins
Indomethacin
NG-Nitroarginine Methyl Ester
Oxygen
Ryanodine
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