Inhibition of Angiotensin‐Converting Enzyme Increases Oestradiol Production in Ewes Submitted to Oestrous Synchronization Protocol

Abstract

This study aimed at evaluating the effects of angiotensin-converting enzyme inhibitor (enalapril) and angiotensin II antagonist (valsartan) on the oestradiol and progesterone production in ewes submitted to oestrous synchronization protocol. The animals were weighed and randomly divided into three groups (n = 7). A pre-experiment conducted to verify the effectiveness and toxicity of enalapril (0.5 mg/kg LW) and valsartan (2.2 mg/kg LW) showed that, in the doses used, these drugs were effective in reducing blood pressure without producing toxic effects. In the experiment, all animals were subjected to oestrous synchronization protocol during 12 days. On D10, D11 and D12, animals received saline, enalapril or valsartan (same doses of the pre-experiment), according to the group randomly divided. The hormonal analysis showed an increase in oestradiol on the last day of the protocol (D12) in animals that received enalapril (p < 0.05), but not in other groups, without changing the concentration of progesterone in any of the treatments. It is concluded that valsartan and enalapril are safe and effective subcutaneously for use in sheep and that the angiotensin-converting enzyme (ACE) inhibition with enalapril leads to an increase in oestradiol production near ovulation without changing the concentration of progesterone. This shows that ACE inhibition may be a useful tool in reproductive biotechnologies involving induction and synchronization of oestrus and ovulation in sheep.

ACE inhibition in goats under fixed‐time artificial insemination protocol increases the pregnancy rate and twin births

“…One of the key points to explain these results may be the increase in the estradiol production through the inhibition of the ACE with the use of enalapril. In another study of our research group, we found results that show that enalapril, when used in a TAI protocol in sheep, led to an increase in estradiol on D12 of TAI protocol (Costa et al., ). In this case, the increase in estradiol occurred in the pre‐ovulatory period, in which a peak of estradiol occurs (Saifillizam, Routly, Smith, & Dobson, ) and which induces the peak of LH followed by ovulation (Moraes, Souza, & Gonçalves, ).…”

“…One of the key points to explain these results may be the increase in the estradiol production through the inhibition of the ACE with the use of enalapril. In another study of our research group, we found results that show that enalapril, when used in a TAI protocol in sheep, led to an increase in estradiol on D12 of TAI protocol (Costa et al, 2014).…”

Impact Of Hypotensive Action Of Angiotensin Converting Enzyme Inhibitor On Ovarian-Intraovarian Blood Flow And Follicles Development In Goats Hormonally Stimulated With Repeated Fsh-Ecg Treatment

“…Ovaries and follicles B-mode ultrasonography was performed each 24 h (each 12 h on the days of FSH/eCG administration); and used to measure all ovarian antral follicles. For measurement of structures of interest, including the growth pattern of the ovarian follicles, ultrasonographic examinations were recorded as videos, followed by the capture and measurement of images (with several different projections of ovary) using the Image J® software 7 , which was previously calibrated. The mean diameter (average of two dimensions, vertical and horizontal) of each identified follicle was taken from images.…”

“…The settings of the scanner (Doppler sampling frequency (PRF) = 1.7 kHZ and color gain = 70% or just below the background noise level recorded in a motionless animal) remained constant for the duration of the study. Both arbitrary-scale [Absence (AB); Low (LO) and Moderate-high (MH) ( Figure 2) and quantitative analysis of the blood flow area (ImageJ ® ) 7 were used to assess the intraovarian blood flow in Doppler images, as described by Oliveira et al [24], with modifications. Briefly, in the images containing the cross-sectional area of the ovary with the strongest color Doppler signal, the ovary was out-lined manually and the total ovarian area (TA) recorded.…”

“…Ang-1-7 is generated from Angiotensin I or II by endopeptidases [14] and, although its production may be independent of ACE, it is known that the use of an ACE inhibitor would prevent the conversion of Angiotensin I into Angiotensin II, increasing the production of Ang-1-7 [5]. Higher levels of this peptide have been found in the follicular phases of rats [7]. Moreover, a greater presence of Angiotensin II has been observed in atrophic [8] and dominant follicles [13], showing that Angiotensin II and Ang-1-7 play a fundamental role in follicular development and atresia.…”