Influence of isoprostanes on vasoconstrictor effects of noradrenaline and angiotensin II

The isoprostanes, 8-iso-prostaglandin F-2 alpha and 8-iso-prostaglandin E-2, which are released in vivo by free radical-catalyzed peroxidation of arachidonic acid, are potent vasoconstrictors. Increased formation of 8-iso-prostaglandin F-2 alpha 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 A(2) mimetic, U 46619, and with the isoprostanes, 8-iso-prostaglandin F-2 alpha, 8-iso-prostaglandin E-2, 8-iso-prostaglandin E-1 and 8-iso-prostaglandin F-3 alpha, 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 E-2 and 8-iso-prostaglandin F-2 alpha, 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 F-2 alpha 8-iso-prostaglandin E-2 and 8-iso-prostaglandin E-1, which were applied as a bolus, induced much more pronounced vasoconstrictions than prostaglandin F-2 alpha prostaglandin E-2 and prostaglandin F-3 alpha. Prostaglandin E-1 and 8-iso-prostaglandin F-3 alpha showed no effects. In conclusion, it can be assumed that the powerful vasoconstrictions induced by 8-iso-prostaglandin E-2 and 8-iso-prostaglandin F-2 alpha and their potentiating effects on vasoconstrictions induced by noradrenaline or angiotensin II might be of pathophysiological relevance in cardiovascular diseases. (C) 1999 Elsevier Science B.V. All rights reserved.