Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent.
The main aim of this study was to determine the effects of endothelium removal on tension and intracellular Ca(2+) ([Ca(2+)](i)) during hypoxic pulmonary vasoconstriction (HPV) in rat isolated intrapulmonary arteries (IPA). Rat IPA and mesenteric arteries (MA) were mounted on myographs and loaded with the Ca(2+)-sensitive fluorophore fura PE-3. Arteries were precontracted with prostaglandin F(2alpha), and the effects of hypoxia were examined. HPV in isolated IPA consisted of a transient constriction superimposed on a second sustained phase. Only the latter phase was abolished by endothelial denudation. However, removal of the endothelium had no effect on [Ca(2+)](i) at any point during HPV. The endothelin-1 antagonists BQ-123 and BQ-788 did not affect HPV, although constriction induced by 100 nM endothelin-1 was abolished. In MA, hypoxia induced an initial transient rise in tension and [Ca(2+)](i), followed by vasodilatation and a fall in [Ca(2+)](i) to (but not below) prehypoxic levels. These results are consistent with sustained HPV being mediated by an endothelium-derived constrictor factor that is distinct from endothelin-1 and that elicits vasoconstriction via Ca(2+) sensitization.
Robertson
Tom P
TP
Department of Physiology and Pharmacology, Institute of Comparative Medicine, University of Georgia, Athens, Georgia 30602-7389, USA. troberts@vet.uga.edu
Aaronson
Philip I
PI
Ward
Jeremy P T
JP
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium