Experimental diabetes: reduction of serotonin-induced vasoconstriction by meclofenamic acid in vitro

In diabetes the sensitivity of isolated rat aortae to serotonin is greatly diminished and the dose-response curve is shifted to the right. The maximal response is reduced to 37% of control, the threshold dose is approximately tenfold greater, and the ED50 is about fourfold greater than control. This decrease in sensitivity may be due, in part, to a reduction in the synthesis of prostaglandins because serotonin-induced responses in normal and diabetic arteries treated with meclofenamate are also significantly diminished. In addition, there is evidence that both receptor-operated Ca2+ and potential-operated Ca2+ channels may be impaired because the responses to norepinephrine and KCl are both dampened in diabetic aortae. The greatly diminished effect of serotonin may be a sensitive tool to study the nature of diabetes better and to monitor its development.