Measurement of endothelial cytosolic calcium concentration and nitric oxide production reveals discrete mechanisms of endothelium-dependent pulmonary vasodilatation.
Nitric oxide is an endothelium-derived relaxing factor. Conversion of L-arginine to nitric oxide follows mediator-induced elevation of endothelial cytosolic calcium concentration. However, not all endothelium-dependent vasodilatation is caused by endothelium-derived relaxing factor, and few studies have correlated changes in vascular tone with measurement of free cytosolic calcium concentration or nitric oxide. The effects of three endothelium-dependent vasodilators (acetylcholine, bradykinin, and A23187) on vascular tone and nitric oxide production were studied in proximal rat pulmonary artery rings. Changes in free cytosolic calcium concentration and nitric oxide production were also studied in bovine pulmonary artery endothelial cells. A23187 and bradykinin caused pulmonary vasodilatation, nitric oxide production, and elevation of endothelial calcium concentrations. Although acetylcholine caused endothelium-dependent vasodilatation, it reduced free cytosolic calcium concentration and failed to increase nitric oxide levels. Acetylcholine-induced dilatation was partially inhibited by meclofenamate but was unaffected by ouabain. Acetylcholine, unlike bradykinin and A23187, does not act through a nitric oxide-dependent mechanism in the rat pulmonary vasculature.
Archer
S L
SL
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN 55417.
Cowan
N J
NJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003470:Culture Media; D003600:Cytosol / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000502:physiology*
D003470:Culture Media; D009569:Nitric Oxide; D002118:Calcium