Influence of isoprostanes on vasoconstrictor effects of noradrenaline and angiotensin II

The isoprostanes, 8-iso-prostaglandin F2alpha and 8-iso-prostaglandin E2, which are released in vivo by free radical-catalyzed peroxidation of arachidonic acid, are potent vasoconstrictors. Increased formation of 8-iso-prostaglandin F2alpha has been detected in human cardiovascular diseases, in which enhanced plasma levels of noradrenaline and angiotensin II have harmful vasoconstrictor effects. Therefore, we investigated the influence of perfusions with the thromboxane A2 mimetic, U 46619, and with the isoprostanes, 8-iso-prostaglandin F2alpha, 8-iso-prostaglandin E2, 8-iso-prostaglandin E1 and 8-iso-prostaglandin F3alpha, on the vasoconstrictor effects of noradrenaline and angiotensin II in the isolated perfused rabbit ear. Our results demonstrate that perfusions with U 46619, 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2alpha, at a subthreshold concentration (30 nM), amplified the vasoconstrictions induced by noradrenaline or angiotensin II significantly. In addition, the results show that U 46619, 8-iso-prostaglandin F2alpha, 8-iso-prostaglandin E2 and 8-iso-prostaglandin E1, which were applied as a bolus, induced much more pronounced vasoconstrictions than prostaglandin F2alpha, prostaglandin E2 and prostaglandin F3alpha. Prostaglandin E1 and 8-iso-prostaglandin F3alpha, showed no effects. In conclusion, it can be assumed that the powerful vasoconstrictions induced by 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2alpha and their potentiating effects on vasoconstrictions induced by noradrenaline or angiotensin II might be of pathophysiological relevance in cardiovascular diseases.