It has been recently reported that the oestrogen receptor (ER) alpha agonist PPT (4,4’,4’’-(4-propyl-[1H]-pyrazole-1,3,5-triyl) tris-phenol) is more potent than the ER-beta receptor agonist DPN (2,3-bis(4-hydroxyphenyl)-propionitrile) at producing relaxations in rat mesenteric artery (Montgomery et al., 2003). We have investigated the relaxant actions of the ER-alpha agonist PPT and the ER-beta agonist DPN in aorta from rat and aorta and mesenteric artery from mouse.

Aorta was obtained from female Wistar rat (250-350g) and C57 wild-type (WT) and NOS-3-KO mouse (24-32g) and mesenteric artery from female WT mouse. Rings of blood vessel were set up in small vessel myographs (except rat aorta: conventional organ bath) for recording of isometric contractions. For rat aorta, some tissues were gently rubbed to remove endothelium. Tissues were contracted with KCl (40 mM) and tested for relaxations to acetylcholine, then again contracted with KCl and tested for relaxations to increasing cumulative concentrations of ER agonists.

In rat aortic rings, the ER-beta agonist DPN (30 µM) produced significantly greater relaxations of KCl evoked contractions than the ER-alpha agonist PPT (30 µM) (66.4±8.5% versus 27.8±5.4% relaxation, respectively, n=6). Relaxations to DPN also occurred in endothelium-denuded aorta from rat (30 µM: 50.2±2.0%, n=5, not significantly different from effect in presence of endothelium).

In WT mouse aorta, the same result was found: the ER-beta agonist DPN (100 µM) produced significantly greater relaxations of KCl evoked contractions than the ER-alpha agonist PPT (100 µM) (42.2±6.8%, n=6 versus –9.1±4.1% relaxation, n=5; for DPN and PPT, respectively). Relaxations to DPN also occurred in aorta from NOS-3-knockout mice (100µM: 72.6±8.0%, n=6). PPT failed to produce relaxations in mouse aorta, but in WT mouse mesenteric artery, PPT was significantly more potent than DPN at producing relaxations of KCl evoked contractions (10 µM: 33.5±13.4%, n=4 versus 8.9±4.7% relaxation, n=7, for PPT and DPN, respectively).

In the mouse mesenteric artery, as in the rat mesenteric artery, PPT is more potent than DPN at producing relaxations; however, the reverse is true in the rat and mouse aorta. Effects of ER receptor subtype selective agonists are tissue dependent, and are largely NO/endothelium independent.

Montgomery, S. et al. (2003). Br. J. Pharmacol. 139, 1249-1253