Response: Angiotensin II: Does It Have a Direct Obligate Role in Ovulation?

Department of Obstetrics and Gynecology, Yale University, New Haven, CT 06510-8063.
Science (Impact Factor: 33.61). 09/1989; 245(4920):870-1. DOI: 10.1126/science.245.4920.871
Source: PubMed
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    • "Ovulation is inhibited by the administration of saralasin to in vitro perfused rabbit ovaries (Yoshimura et al. 1993). However, in rat, Ang II receptors were not detected in every developing follicle (Husain et al. 1987) and in preovulatory follicles with LH receptors (Daud et al. 1989), suggesting a species-specific effect of Ang II on ovulation. Cattle provide an excellent model for studying the ovulatory process, since the follicular environment can be easily modified by ultrasound-guided intrafollicular injection (Kot et al. 1995, Ginther et al. 2004) and accurately monitored on a day-to-day basis by ultrasonography in vivo (Savio et al. 1988, Ginther et al. 1989, Evans & Fortune 1997). "
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    ABSTRACT: There is evidence that the renin-angiotensin system plays an important role in ovulation in cattle. Using an in vivo model, we investigated the role of angiotensin (Ang) II in bovine ovulation by injecting Ang II receptor antagonists into ovulatory follicles. Animals (n = 102) were pre-synchronized and, when the follicles reached 12 mm, they were given the respective treatment and the cows received GnRH agonist (i.m.) to induce ovulation. The ovulation rate was significantly lower when 100 mu M saralasin (Ang II receptor antagonist) was intrafollicularly injected (14.3%) in comparison with saline solution (83.3%). Based on these results, a second experiment was carried out to determine the timing of Ang II's critical role in ovulation. Saralasin inhibited ovulation only when applied at 0 and 6 h (16.7 and 42.9% ovulation rate in the 0- and 6-h groups respectively), but not at 12 h (100%) following GnRH agonist treatment. To investigate the subtypes of Ang II receptors implicated in the LH-induced ovulation, losartan (LO; AT(1)-Ang II receptor antagonist), PD123 319 (AT(2)-Ang II receptor antagonist), LO+PD123 319, or saline were intrafollicularly injected when the cows were challenged with GnRH agonist. Ovulation was inhibited by PD123 319 and LO+PD123 319 (50.0 and 33.3% on ovulation rate respectively), but not by LO or saline solution (100% ovulation in both groups). From these results, we suggest that Ang II plays a pivotal role in the early mechanism of bovine ovulation via the AT(2) receptor subtype.
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    ABSTRACT: 1. In previous studies we have demonstrated and solved several methodological problems in relation to the measurement of prorenin by trypsin activation in rat, bovine, hog and horse plasma. 2. The aim of the present study was to develop a method for the measurement of prorenin in bovine and porcine ovarian follicular fluid. 3. Trypsin activation of follicular fluid generated angiotensin I immunoreactive material (AI IM) in both species. 4. The AI IM interfered with the renin assay, but could be completely removed by a cation exchange resin in a batch-wise technique. 5. The enzymatic activity of trypsin-activated prorenin and pre-existing active renin was completely inhibited by a specific inhibitor of renin. 6. The reactions were optimized and an accurate measurement of prorenin in ovarian follicular fluid was developed. 7. The existence of prorenin and renin in bovine ovarian follicular fluid was established. Prorenin and renin in porcine ovarian follicular fluid was demonstrated for the first time. 8. The ratio between ovarian follicular fluid and plasma was 43 for prorenin and 19 for active renin in cattle. The same ratios in pigs were 1.3 and 0.4, respectively. These findings indicate a species difference with respect to the amount of prorenin or active renin present in ovarian follicular fluid.
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