Influence of isoprostanes on vasoconstrictor effects of noradrenaline and angiotensin II

• Published in: European journal of pharmacology Vol. 378; no. 1; pp. 47 - 55
• Main Authors: Sametz, Wolfgang, Grobuschek, Tanja, Hammer-Kogler, Susanne, Juan, Heinz, Wintersteiger, Reinhold
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.07.1999; Elsevier
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Angiotensin II; Angiotensin II - pharmacology; Animals; Biological and medical sciences; Blood and lymphatic vessels; Bridged Bicyclo Compounds, Heterocyclic; Cardiology. Vascular system; Dinoprost - analogs & derivatives; Dinoprost - pharmacology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Drug Interactions; Ear; F2-Isoprostanes; Fatty Acids, Unsaturated; Female; Hydrazines - pharmacology; Isoprostane; Male; Medical sciences; Noradrenaline; Norepinephrine - pharmacology; Perfusion; Prostaglandin; Prostaglandins - pharmacology; Rabbits; Regional Blood Flow - drug effects; U 46619; Vasoconstriction; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Isoprostane; U 46619; Prostaglandin; Angiotensin II; Noradrenaline; Vasoconstriction; Potentiation; Pathogenesis; Rabbit; Cardiovascular disease; Lagomorpha; Catecholamine; In vitro; Isolated organ; Vertebrata; Mammalia; Blood vessel; Animal; Ear; Vasoconstrictor agent; Norepinephrine; Circulatory system; Mechanism of action; Prostaglandin derivatives
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00437-9

The isoprostanes, 8- iso-prostaglandin F 2α 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 2α 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 2α, 8- iso-prostaglandin E 2, 8- iso-prostaglandin E 1 and 8- iso-prostaglandin F 3α, 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 2α, 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 2α, 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 2α, prostaglandin E 2 and prostaglandin F 3α. Prostaglandin E 1 and 8- iso-prostaglandin F 3α 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 2α and their potentiating effects on vasoconstrictions induced by noradrenaline or angiotensin II might be of pathophysiological relevance in cardiovascular diseases.