Pulmonary arterial hypoxic contraction: signal transduction.
The response of isolated rat pulmonary arteries to acute hypoxia has previously been reported to be biphasic, consisting of an initial rapid contraction of short duration, followed by partial relaxation (phase 1) and then a second slowly developed but sustained contraction (phase 2). The purpose of this study was to determine the following: 1) whether products from the endothelium might be required, 2) whether extra- and/or intracellular calcium or protein kinase C might be second messengers in mediating the pulmonary arterial hypoxic contraction, and 3) whether or not guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived relaxing factor (EDRF), prostaglandin I2 (PGI2) or A2 adenosine receptor activation is involved in phase 1 relaxation. Neither Ca(2+)-free media nor verapamil (a Ca2+ channel blocker) altered the phase 1 contraction, but the phase 2 contraction was abolished by either of these treatments. Ryanodine (a sarcoplasmic reticulum Ca2+ depleter) had no effect on phase 1 contraction. H-7 (a PKC inhibitor) inhibited the phase 2 contraction, whereas it had no effect on phase 1 contraction. Removal of the endothelium abolished phase 1 contraction in either Ca(2+)-free media or normal Ca2+ media but did not alter phase 2 contraction or phase 1 relaxation. Neither methylene blue (guanylate cyclase inhibitor), N omega-nitro-L-arginine, (EDRF blocker), acetylsalicylic acid (cyclooxygenase inhibitor), xanthine amino congener (adenosine receptor blocker), nor glybenclamide blocked the phase 1 relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction; D014664:Vasodilation
D000317:Adrenergic alpha-Antagonists; D011493:Protein Kinase C; D002118:Calcium