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.
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.
Bing
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Department of Obstetrics and Gynoecology, University Hospital, Nottingham, UK.
Johnson
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Broughton Pipkin
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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
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D019808:Losartan