ANGIOTENSIN RECEPTORS IN MYOMETRIUM AND MYOMETRIAL VESSELS FROM UTERIOF 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 m embrane fractions from myometrial samples obtained at non-pregnant hys terectomy in women of reproductive age, Specific binding was also meas ured in paired samples of vascular and 'vessel-free' myometrium. 2. A single class of high-affinity receptor sites was identified in the tot al myometrial preparations (n = 10), with a median equilibrium dissoci ation constant (K-d) of 0.122 nmol/l (range 0.065-0.465 nmol/l) and co ncentration of receptor sites (B-max) of 149 fmol/mg protein (range 10 5-435 fmol/mg), Receptor characterization studies using losartan (an a ngiotensin type 1 receptor antagonist) and PD123177 (an angiotensin ty pe 2 receptor antagonist) showed the myometrium to contain almost enti rely type 2 receptors, 3. The median K-d and B-max for specific angiot ensin 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 myomet rium (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 I-125-labelled ang iotensin II in 'vessel-free' myometrium was higher in samples from the follicular phase than in samples from the luteal phase (median 144 co mpared with 37 fmol/mg; P < 0.02), A similar trend was found in the ve ssels themselves, but this failed to reach statistical significance (4 59 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 (sec retory) phase is a preparation for pregnancy, removing an inhibitory f actor to uterine growth and vascularization and allowing greater prost acyclin synthesis.