Effects of U46619 on intracellular Ca++ concentration and tension in human umbilical artery

The aim was to examine the effects of U46619, a thromboxane A2 analog, on intracellular Ca++ concentration and tension in human umbilical artery.

By means of front-surface fluorometry and human umbilical arterial strips loaded with fura-2 we simultaneously measured intracellular Ca++ concentration and tension.

In the presence of extracellular Ca++ (1.25 mmol/L), U46619 elevated intracellular Ca++ concentration and tension in a concentration-dependent manner. Oscillations of both intracellular Ca++ concentration and tension were evident in many cases. In the absence of extracellular Ca++ U46619 induced a transient elevation of intracellular Ca++ concentration that was associated with a transient increase and a sustained tension. At any given intracellular Ca++ concentration level the tension induced by the cumulative application of extracellular Ca++ during depolarization with high external K+ in the presence of U46619 was greater than that in the absence of this drug; thus the intracellular Ca++ concentration-tension relationship in the presence of U46619 shifted to the left.

The tension developed by U46619 depends both on an influx of Ca++ from the extracellular space and on release of intracellular Ca++, and U46619 increased Ca++ sensitivity of the contractile apparatus.