Involvement of Angiotensin II in the Process of Gonadotropin-lnduced Ovulation in Rabbits

Abstract

In the present study we investigated the role of angiotensin II (Ang II) receptor subtypes in gonadotropin-induced ovulation, oocyte maturation, and ovarian steroidogenesis and prostaglandin (PG) production in in vitro-perfused rabbit ovaries. The addition to the perfusate of PD123319, a nonpeptide Ang II antagonist with a high affinity for AT2 receptors, inhibited hCG-induced ovulation in a dose-dependent manner, whereas CV-11974, a nonpeptide AT1 receptor antagonist, had no effect. The majority of ovulated ova and follicular oocytes resumed meiotic maturation in response to hCG; and PD123319, but not CV-11974, significantly inhibited hCG-induced oocyte maturation. The addition of both Ang II receptor antagonists to the perfusate had no significant effect on the concentration of progesterone in the perfusate of hCG-treated ovaries, whereas PD123319 inhibited the hCG-stimulated production of estradiol. The production of PGE2 and PGF2 alpha was significantly increased at 6 h in hCG-treated ovaries compared with ovaries before hCG administration. PD123319 inhibited the hCG-stimulated production of PGs by perfused rabbit ovaries in a dose-dependent manner, indicating that hCG-induced PG synthesis is mediated, at least in part, via the activation of AT2 receptors. Ovulatory efficiency in ovaries perfused with or without PD123319 in the presence of hCG was significantly correlated with PG production by perfused rabbit ovaries 12 h after exposure to hCG (r = 0.6553 for PGE2, p < 0.001; r = 0.4758 for PGF2 alpha, p < 0.05). In conclusion, Ang II exerts complex and coordinated control on at least two distinct aspects in the normal ovulatory process, ovulation and oocyte maturation. Ang II produced locally by gonadotropin exposure may be a part of a novel intraovarian paracrine or autocrine control mechanism that operates via the AT2 receptor in the ovary.

Evidence that the effect of angiotensin II on bovine oocyte nuclear maturation is mediated by prostaglandins E2 and F2α

“…The results of experiment II and III together strongly suggest that saralasin has no toxic effect on oocyte nuclear and cytoplasmatic maturation. Furthermore, this peptide has been widely used to block the effects of the RAS with high specificity for the AngII receptors (Kuji et al 1996, Camargo & Saad 1999, Ferreira et al 2007. The high rate of embryo development demonstrates that saralasin did not change the kinetics of oocyte nuclear and cytoplasmatic maturation.…”

“…Saralasin was used as a potent AngII antagonist to block all the receptor subtypes (Kuji et al 1996. A saralasin concentration of 10 mM has been used as an effective inhibitor of AngII action (Kuji et al 1996).…”

“…A saralasin concentration of 10 mM has been used as an effective inhibitor of AngII action (Kuji et al 1996). In experiment II, it was demonstrated that saralasin had no detrimental effects on follicular cells.…”

“…The classic effects of AngII regarding the muscular contraction, aldosterone secretion, and sanguineous pressure regulation are mediated by the AngII receptor type 1. In fact, the AngII receptor type 2 has been demonstrated to be the mediator of several reproductive functions including steroidogenesis, oocyte maturation, and ovulation (Kuji et al 1996, Ferreira et al 2007. In cows, the AngII receptor type 2 is present in the dominant follicle (Schauser et al 2001), and its mRNA expression was positively correlated with estradiol production (Portela et al 2006).…”

Angiotensina-(1-7) durante o processo inicial na cascata da ovulação em bovinos

“…Esses resultados sugerem que, ao contrário da Ang II (KUJI et al, 1996;FERREIRA et al, 2007), a Ang-(1-7) parece não ser necessária, nem essencial para desencadear o processo de ovulação em bovinos.…”