Role of the angiotensin II system in regulation of ovulation and blood flow in the rat ovary

Abstract

The aim of the present study was to examine the roles of the angiotensin II receptor subtypes, AT 1 and AT 2 , in ovulation, and to evaluate the contribution of angiotensin II-mediated pathways in regulation of ovarian blood flow. The AT 1 -specific antagonist, losartan, was administered alone or in combination with the AT 2 -specific antagonist, PD123319, to preovulatory rat ovaries perfused in vitro. Losartan (100 mol l − 1 ) did not affect the number of ovulations, whereas the combination of losartan (100 mol l − 1 ) and PD123319 (10 mol l − 1 ) inhibited ovulation. The angiotensin II antagonists did not affect the ovarian production of oestradiol, progesterone, prostaglandin E 2 (PGE 2 ), PGF 2␣ or plasminogen activator activity. Ovarian nitric oxide production was inhibited by losartan. Ovarian blood flow was measured by laser Doppler flowmetry in vivo in preovulatory rat ovaries. Intrabursal injection of angiotensin II reduced ovarian blood flow of gonadotrophin-stimulated rats. Losartan had no effect on basal ovarian blood flow but completely blocked the angiotensin II-induced reduction. In contrast, treatment with PD123319 increased basal ovarian blood flow and failed to reverse the effect of exogenously administered angiotensin II, indicating that under physiological conditions, ovarian blood flow of the rat is negatively regulated by angiotensin II mainly through the action of AT 2 . Taken together, these results indicate that two different types of angiotensin II receptor facilitate ovulation by cooperative mechanisms and that they regulate ovarian blood flow in a different manner.

Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances

“…However, a selective nonpeptide antagonist for AGTR2 receptors (PD123,319) had no effects on the ovulation rate in in vitro-perfused rat ovaries (Mikuni et al 1998). Furthermore, the administration of PD123,319 diminished but did not completely block ovulation in rats (Mitsube et al 2003). Taken together, these results indicate that Ang II is essential for ovulation in rats, but this effect is not exclusively regulated via the AGTR2.…”

Angiotensin II induces apoptosis in human mural granulosa-lutein cells, but not in cumulus cells

“…As mentioned above, the preovulatory increase in intrafollicular AngII may facilitate oocyte maturation (42) and ovulation (9,44) or the production of progesterone by human GL cells (45). Angiotensin II is increased in both follicular atresia (36,37) and corpus luteum regression (46), events that are known to be linked to apoptosis (47)(48)(49)(50)(51)(52)(53).…”

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

“…It seems that AT 1 receptormediated medullary vasodilator response to low doses of ANG II is mainly due to the release of PGs, whereas the dilator response to high doses has additional NO-and kinin-dependent components. Losartan had no effect on basal ovarian blood flow in rats but blocked the ANG II-induced flow reduction, and, in contrast, the AT 2 receptor antagonist PD123319 increased ovarian basal blood flow and failed to reverse the effect of exogenous ANG II, indicating that under physiological conditions, ovarian blood flow of the rat is negatively regulated by ANG II through AT 2 receptors (Mitsube et al, 2003). Bayraktutan and Ulker (2003) suggested that ANG II stimulates NO production in rat coronary microvascular endothelial cells in both an AT 1 -and AT 2 -receptorregulated manner.…”