Indomethacin enhances endothelial NO release — evidence for a role of PGI2 in the autocrine control of calcium-dependent autacoid production

摘要: Objective: We studied whether NO or prostacyclin (PGI2), which are continuously released by endothelial cells, have autocrine/paracrine effects on the calcium-dependent autacoid production modulating intracellular Ca2+ concentration ([Ca2+]i). Methods: Histamine(His)-induced [Ca2+]i increases (Fura 2-method) and NO-dependent cGMP increase were measured in human umbilical vein cells (HUVECs) before after cyclooxygenase inhibition application of cAMP- cGMP-elevating drugs. Results: 0.3 μM His increased from 77±2 nM to 418±59 nM. The His-induced significantly attenuated following treatment with PGI2 (by 23%) forskolin 33%), both increasing cAMP release HUVECs 49% 66%). inhibited protein kinase A-activator cBIMPS 61%) also abolished release. Conversely, indomethacin augmented 32%), resulting a as indicated an enhanced LNNA-sensitive HUVECs. In contrast, neither (basal 0.4±0.1 pmol/mg) elicited 10 SNP (21±2 C-type natriuretic peptide (CNP, 4.6±1.6 nor its reduction 30 LNNA had any effect increases. Conclusion: attenuates agonist-induced cAMP-dependent mechanism, thereby not only own synthesis via negative feedback but that NO. Consequently, reduced levels result production. does cause control might therefore compensate for lack PGI2.