Angiotensin converting enzyme inhibition of the gonadotropin-stimulated rabbit: effect on estradiol production.
OBJECTIVE
Our purpose was to determine whether angiotensin converting enzyme (ACE) inhibitors affect gonadotropin-stimulated estradiol (E2) production.


METHODS
This was a prospective, masked, randomized, placebo-controlled animal trial. Twenty female New Zealand White rabbits were hyperstimulated with gonadotropins. One-half of the rabbits received concomitant treatment with the ACE inhibitor, enalapril; one-half received concomitant treatment with a placebo.


RESULTS
Baseline peripheral E2 (13 +/- 4 vs 11 +/- 2 pg/ml) and angiotensin II (Ang II) (22 +/- 5 vs 27 +/- 7 pg/ml) levels were similar in both groups. Significant inhibition of peripheral Ang II levels was achieved in the enalapril group (32 +/- 6 vs 93 +/- 15 pg/ml; P = 0.005). E2 was significantly higher in the rabbits receiving enalapril versus placebo (369 +/- 58 vs 183 +/- 35 pg/ml, P < 0.03), respectively. By day 10, peripheral E2 had returned to normal levels in both groups (13 +/- 1 vs 13 +/- 1 pg/ml). However, E2 levels in the ovarian effluent were 2.8 times higher in the enalapril rabbits.


CONCLUSIONS
Peripheral Ang II levels increase after gonadotropin stimulation and ACE inhibitors are able to blunt this increase significantly. ACE inhibition has a significant stimulatory effect on ovarian E2 production. This implies that Ang II may normally inhibit ovarian E2 production in stimulated cycles.
Division of Reproductive Endocrinology, University of Southern California School of Medicine, Los Angeles County Women's and Children's Hospital, USA.
R S
RS
Morris
I L
IL
Wong
R J
RJ
Paulson
D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood*; D005260:Female; D006062:Gonadotropins / Q000494:pharmacology*; D016471:Ovarian Hyperstimulation Syndrome / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D011446:Prospective Studies; D011817:Rabbits; D011863:Radioimmunoassay; D011897:Random Allocation
D000806:Angiotensin-Converting Enzyme Inhibitors; D006062:Gonadotropins; D000804:Angiotensin II; D004958:Estradiol; D004656:Enalapril