title: Female sex steroids increase adrenomedullin-induced vasodilation by increasing the expression of adrenomedullin2 receptor components in rat mesenteric artery.
abstract: Based on the favorable effects of female sex steroids in vascular functions and the potent hypotensive effects of adrenomedullin (AM), we hypothesized that AM-induced vasodilation is gender dependent, and female sex steroids enhance this effect. In endothelium-intact rat mesenteric artery, AM (1 nm-0.3 microM)-induced concentration-dependent relaxation was significantly (P < 0.05) higher in females [pD2(-log EC50 of the molar concentration), 7.05 +/- 0.10; maximal relaxation response (Emax), 69.2 +/- 3.46%] than males (pD2, 6.53 +/- 0.08; Emax, 53.28 +/- 4.86%). The increased relaxation was lost when the females were ovariectomized (OVX) (pD2, 6.14 +/- 0.24; Emax, 39.68 +/- 5.68%). The reduced relaxation response in OVX rats was reversed by administration of either progesterone (P4; pD2, 7.18 +/- 0.07; Emax, 72.4 +/- 2.76%) or 17beta-estradiol (E2; pD2, 7.00 +/- 0.14; Emax, 70.4 +/- 4.79%). AM mediates its effects through either AM(22-52)-sensitive AM1 receptors [composed of calcitonin receptor-like receptors (CLs) and receptor activity-modifying protein (RAMP)2] or AM2 receptors (CL/RAMP3), which can be antagonized more potently by calcitonin gene-related peptide(8-37) than AM(22-52). Pharmacological characterization suggested the involvement of AM2 receptors in the increased vasodilatory effect of AM in both P4- and E2-treated animals as calcitonin gene-related peptide(8-37) (10 microM) was more potent in antagonizing the AM effects (Emax, P(4): 25.92 +/- 5.32%; E2: 29.11 +/- 7.41%) than AM(22-52) (100 microM). RT-PCR studies also supported the involvement of AM2 receptors because expression of mRNA levels encoding CL (previously reported) and RAMP3 were increased in P4- or E2-treated OVX rats. In conclusion, AM-induced vasodilation is gender-dependent and increased by female sex steroids by increased expression of AM2 receptor components.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-1062, USA.
authors.forename: Gracious R
authors.initials: GR
authors.lastname: Ross
authors.forename: Madhu
authors.initials: M
authors.lastname: Chauhan
authors.forename: Pandu R
authors.initials: PR
authors.lastname: Gangula
authors.forename: Luckey
authors.initials: L
authors.lastname: Reed
authors.forename: Chandra
authors.initials: C
authors.lastname: Thota
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D010455:Peptides; D053607:Adrenomedullin; D011374:Progesterone; D004958:Estradiol