Inositol trisphosphate is involved in norepinephrine- but not in hypoxia-induced pulmonary arterial contraction.
The role that second messengers play in pulmonary vasoconstriction is not understood. The purpose of this study was to directly measure inositol phosphates in isolated pulmonary arterial preparations before and during norepinephrine (NE) stimulation and acute hypoxia. Rat main pulmonary arteries were isolated and incubated with myo-[3H]-inositol. After incubation, control tissue was stimulated with 0.5 microM NE or 30 mM KCl. Test preparations were precontracted with 30 mM KCl and then exposed to hypoxia. Samples were homogenized and applied to a high-pressure liquid chromatography column for analysis of inositol phosphates. Results show that inositol trisphosphate (IP3) increases twofold at 5 s following NE stimulation. Thirty micromolars of KCl results in a slight but significant increase in IP3 formation at 5 min following the stimulation. Phentolamine inhibits the KCl-induced increase in IP3 formation, whereas A23187 has no effect on IP3 levels. Hypoxia caused a biphasic contraction in the precontracted isolated rat pulmonary artery. IP3 levels did not change during the hypoxic period. In conclusion, NE causes a rapid increase in IP3 formation consistent with the time course of production of an excitation-contraction coupling second messenger. However, inositol trisphosphate is not involved in the signal transduction pathway leading to pulmonary arterial contraction induced by hypoxia.
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Department of Physiology/Biophysics, Indiana University School of Medicine, Indianapolis 46202.
Packer
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English
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Rhoades
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D000208:Acute Disease; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D000860:Hypoxia / Q000503:physiopathology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000001:Calcimycin; D011189:Potassium Chloride; D015544:Inositol 1,4,5-Trisphosphate; D009638:Norepinephrine