Comparison of nitric oxide and prostacyclin in endothelium-dependent vasorelaxation of human umbilical artery at midgestation.

Abstract

We intended to compare the relative importance of nitric oxide and prostacyclin as endothelium-derived vasorelaxing factors released by histamine in human umbilical artery at the midstage (18 to 22 weeks) of gestation. By use of very thin muscle strips, which allows rapid diffusional access of applied drugs (in a few seconds), isometric tensions were recorded in response to histamine. The histamine-induced contractions and the relaxing effect of histamine on the potassium chloride (39 mmol/L) contractions were studied in relation to the existence of endothelium, L-NG-nitro arginine, and indomethacin. The relaxing effects of glyceryl trinitrate and prostacyclin on the potassium chloride contractions were also examined. The contractile responses to histamine were more sensitive and the relation tensions of histamine contractions, compared with the 39 mmol/L K(+)-induced contractions, were large in endothelium-denuded strips than in endothelium-intact strips. Histamine contractions were enhanced in endothelium-intact strips in the presence of 10 mumol/L L-NG-nitro arginine (competitive inhibitor of nitric oxide synthase) but not in the presence of 10 mumol/L indomethacin (cyclooxygenase inhibitor). Histamine produced a concentration-dependent relaxation during the maintained contraction induced by 39 mmol/L K+. These histamine-induced relaxations were completely blocked by L-NG-nitro arginine but not by indomethacin. Glyceryl trinitrate and prostacyclin relaxed the sustained contractions induced by 39 mmol/L K+ in a dose-dependent manner; however, the degree of relaxation by glyceryl trinitrate was more prominent than that by prostacyclin. These results suggest that nitric oxide is more potent than prostacyclin as a vasorelaxing substance released from the endothelium and that nitric oxide has an important role for controlling fetoplacental circulation at midgestation.