title: Angiotensin receptors in myometrium and myometrial vessels from uteri of women during the follicular and luteal phases of the menstrual cycle and in late pregnancy.
abstract: 1. Receptors for angiotensin II were identified and characterized in membrane fractions from myometrial samples obtained at non-pregnant hysterectomy in women of reproductive age. Specific binding was also measured in paired samples of vascular and "vessel-free' myometrium. 2. A single class of high-affinity receptor sites was identified in the total myometrial preparations (n = 10), with a median equilibrium dissociation constant (Kd) of 0.122 nmol/l (range 0.065-0.465 nmol/l) and concentration of receptor sites (Bmax) of 149 fmol/mg protein (range 105-435 fmol/mg). Receptor characterization studies using losartan (an angiotensin type 1 receptor antagonist) and PD123177 (an angiotensin type 2 receptor antagonist) showed the myometrium to contain almost entirely type 2 receptors. 3. The median Kd and Bmax for specific angiotensin II binding in isolated myometrial vessel homogenates were 0.086 nmol/l (range 0.060-0.433) and 260 fmol/mg protein (range 197-737 fmol/mg) respectively. Vascular specific binding density was always higher in dissected out myometrial vessels than in paired vessel-free myometrium (median 372 compared with 120 fmol/mg protein; n = 20; P < 0.001). The specific binding in the paired samples was strongly correlated (r = 0.8904, P < 0.0001). 4. The specific binding of 125I-labelled angiotensin II in "vessel-free' myometrium was higher in samples from the follicular phase than in samples from the luteal phase (median 144 compared with 37 fmol/mg; P < 0.02). A similar trend was found in the vessels themselves, but this failed to reach statistical significance (459 compared with 225 fmol/mg; P = 0.051). 5. It is suggested that the down-regulation of the angiotensin type 2 receptors in the luteal (secretory) phase is a preparation for pregnancy, removing an inhibitory factor to uterine growth and vascularization and allowing greater prostacyclin synthesis.
authors.affiliation: Department of Obstetrics and Gynoecology, University Hospital, Nottingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bing
authors.forename: I R
authors.initials: IR
authors.lastname: Johnson
authors.forename: F
authors.initials: F
authors.lastname: Broughton Pipkin
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology; D001808:Blood Vessels / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008183:Luteal Phase / Q000378:metabolism*; D009215:Myometrium / Q000098:blood supply / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D019808:Losartan