FLOW-INDUCED RESPONSES IN CAT ISOLATED PULMONARY-ARTERIES

Isolated, cannulated, endothelium-intact cat pulmonary arteries, avera ging 692 +/- 104 mu m in diameter, were set at a transmural pressure o f 10 mmHg and monitored with a video system. Intraluminal flow was inc reased in steps from 0 to 1.6 ml/min by using a syringe pump. An elect ronic system held pressure constant by changing outflow resistance. Fl ow-diameter curves were generated in physiological saline solution. At constant transmural pressure, the arteries constricted in response to increased intraluminal flow. Constriction was not affected by removin g extracellular Ca2+ but was abolished after treatment with ryanodine to deplete intracellular Ca2+ stores, with the endothelin-l synthesis inhibitor phosphoramidon, with the endothelin A-receptor antagonist BQ -123, with the protein kinase C inhibitor staurosporine, or with gluta raldehyde to reduce endothelial cell deformability. The results indica te that isolated pulmonary arteries can constrict in response to intra luminal flow and suggest that constriction is mediated by endothelin-l and depends on intracellular Ca2+ release and protein kinase C activa tion.