Relaxations to oestrogen receptor subtype selective agonists in rat and mouse arteries.
It has been recently reported that the oestrogen receptor alpha agonist PPT (4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl) tris-phenol) is more potent than the oestrogen receptor beta agonist DPN (2,3-bis(4-hydroxyphenyl)-propionitrile) at producing relaxations in rat mesenteric artery. We have investigated the relaxant actions of PPT and DPN in rat and mouse aorta and mesenteric artery. In rat aortic rings contracted with KCl (40 mM), the oestrogen receptor beta agonist DPN produced significantly greater relaxations than the oestrogen receptor alpha agonist PPT. In wild-type (WT) mouse aorta, the same result was found, but in WT mouse mesenteric artery, as in rat mesenteric artery, DPN was significantly less potent than PPT in females but had similar potency to PPT in males. Relaxations to DPN also occurred in aorta from nitric oxide synthase-3-knockout (NOS-3-KO) mice, and in denuded aorta from both mouse and rat. Hence, in the mouse mesenteric artery, as in the rat mesenteric artery, PPT is at least as potent as DPN at producing relaxations; however, DPN was much more potent than PPT in the rat and mouse aorta. Effects of oestrogen receptor subtype selective agonists are tissue dependent. In addition, actions are largely endothelium-independent.
Al Zubair
Khalid
K
Department of Physiology, Royal College of Surgeons in Ireland, Dublin.
Razak
Adibah
A
Bexis
Sotiria
S
Docherty
James R
JR
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000502:physiology; D047629:Estrogen Receptor beta / Q000819:agonists / Q000502:physiology; D005260:Female; D005838:Genotype; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D011189:Potassium Chloride / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000819:agonists* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D011422:Propionates
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009570:Nitriles; D010636:Phenols; D011189:Potassium Chloride; D011720:Pyrazoles; D011960:Receptors, Estrogen; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat