Actions of 8-Epi Prostaglandin F2α on Isolated Rat Aorta

Abstract

8-epi prostaglandin F2alpha(8-epi PGF2alpha) contracted rat thoracic aorta rings in a concentration-dependent manner in the presence or absence of functional endothelium [median effective concentration (EC50) values, 455+/-52 and 268+/-34 nM, respectively; Student's t test; p=0.006]. U46619 was a more potent agonist with or without functional endothelium (EC50 values, 6.8+/-1.6 and 4.5+/-1.0 nM, respectively). SQ29548 [a thromboxane (TP)-receptor antagonist] inhibited contractions to both 8-epi PGF2alpha and U46619 in a competitive manner, with mean pA2 values of 8.3 and 7.9, respectively. 8-Epi PGF2alpha had a further contractile effect in vessels that had been contracted with noradrenaline and had been shown to possess a functional endothelium. Inhibition of thromboxane synthesis with OKY-046 or blockade of endothelin receptors with bosentan had no effect on responses to 8-epi PGF2alpha or U46619. Preincubation with 8-epi PGF2alpha or noradrenaline shifted the concentration-response curves to U46619 upward at low concentrations of U46619 with no significant change in EC50 values or maximal responses. Reduction of TP-receptor number in rat aorta with dithiothreitol caused a concentration-dependent inhibition of responses to both U46619 and 8-epi PGF2alpha, with no effect on maximal responses and or on the responses to U46619 after the preincubation with 8-epi PGF2alpha. These results indicate that 8-epi PGF2alpha is a potent vasoconstrictor in the rat aorta and are suggestive of an action of 8-epi PGF2alpha at the TP receptor.

Vascular effects of 15-F2t-isoprostane in spontaneously hypertensive rats

“…As was seen in previous studies on normotensive rat aorta (Kromer and Tippins 1998;Wagner et al 1997) and pig coronary artery (Wilson et al 1999), the endothelium modulated 15-F 2t -IsoP vasoconstriction through the release of relaxing factors as demonstrated by the enhanced contractions observed in endothelium denuded rings in both strains. In WKY rats, both pretreatment with L-NA and indomethacin increased 15-F 2t -IsoP-induced contraction.…”

Hypertension increases the participation of vasoconstrictor prostanoids from cyclooxygenase-2 in phenylephrine responses

“…The vascular effect of isoprostanes has been described as involving TP receptors [40,41], therefore these compounds could also be involved in the greater response to phenylephrine in the hypertensive strain. In fact, 8-isoprostane levels were greater in the incubation medium of segments from hypertensive animals; in addition, NS 398 reduced 8-isoprostane production.…”

Vascular Biology of the Isoprostanes

“…However, iPF 2α -III-induced contraction was unaffected by endothelin receptor antagonists in rat aorta [52]as well as human saphenous veins [35]. Because regulation of endothelin synthesis is thought to be at the level of gene transcription, and weak intracellular pools are available for rapid release [53], endothelin is not likely to be involved in iPF 2α -III short-term vasomotor effects in most tissues.…”