ISSN: 2148-4902 | E-ISSN: 2536-4553
Northern Clinics of Istanbul The effects of sacubitril/valsartan and ramipril on the male fertility in hypertensive rats [North Clin Istanb]
North Clin Istanb. 2020; 7(5): 425-432 | DOI: 10.14744/nci.2020.30906

The effects of sacubitril/valsartan and ramipril on the male fertility in hypertensive rats

Duygun Altıntaş Aykan1, Asli Yaylali2, Nadire Eser1, Muhammed Seyithanoğlu3, Selma Yaman4, Ahmet Aykan5
1Department of Pharmacology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
2Department of Histology and Embryology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
3Department of Biochemistry, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
4Department of Biophysics, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
5Department of Cardiology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

OBJECTIVE: Renin angiotensinogen system (RAS) inhibitors, ramipril and sacubitril/valsartan are frequently used in the treatment of cardiovascular diseases. Although they are known as contraindicated during pregnancy in hypertensive women, there is not any outcome of their safety in male fertility after exposure to ramipril or sacubitril/valsartan. In this study, we aimed to evaluate the effects of ramipril and sacubitril/valsartan to highlight their safety in the male fertility in normotensive and hypertensive rats.
METHODS: Adult male normotensive and dexamethasone-induced hypertensive rats were treated with sacubitril/valsartan, ramipril and saline for 18 days. Arterial blood pressures were verified using carotid artery cannulation. Male fertility parameters, including the testis weights, histopathologic scoring of the testis, sperm count, sperm motility, morphology, and serum testosterone levels, were analyzed in treated and nontreated normotensive/hypertensive rats.
RESULTS: Sacubitril/valsartan or ramipril treatments did not reveal a significant difference in sperm production, testicular morphology, and radioimmunoassay of serum testosterone levels compared to the control group. However, sperm motility was significantly reduced in rats under RAS inhibition.
CONCLUSION: This finding was likely mediated by the identification of Ang receptors in the tails of rat sperm given that Ang receptors may play a role in the modulation of sperm motility. Identification of RAS-related proteins involved in sperm motility may help to explain their roles in motility. Our data provide general safety evidence for the male fertilization ability after paternal sacubitril/valsartan and ramipril exposure.

Keywords: Paternal exposure, ramipril; sacubitril-valsartan; spermatozoa.

Sakubitril/valsartan ve ramiprilin hipertansif erkek ratlarda fertilite üzerine etkileri

Duygun Altıntaş Aykan1, Asli Yaylali2, Nadire Eser1, Muhammed Seyithanoğlu3, Selma Yaman4, Ahmet Aykan5
1Department of Pharmacology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
2Department of Histology and Embryology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
3Department of Biochemistry, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
4Department of Biophysics, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
5Department of Cardiology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey

Amaç: Renin anjiyotensinojen sistemi (RAS) inhibitörlerinden ramipril ve sakubitril/valsartan, kardiyovasküler hastalıkların tedavisinde sıklıkla kullanılmaktadır. Hipertansif kadınlarda gebelik sırasında kontrendike oldukları bilinmesine rağmen, ramipril veya sakubitril/valsartanın paternal maruziyet sonrası erkek fertilitesinde ilaç güvenilirliğine dair yeterli veri yoktur. Bu çalışmada, ramipril ve sakubitril/valsartanın normotensif ve hipertansif erkek ratlarda fertilite parametreleri üzerindeki etkilerini değerlendirmeyi amaçladık.
Yöntem: Yetişkin erkek normotansif ve deksametazonla indüklenmiş hipertansif ratlara 18 gün boyunca sakubitril/valsartan, ramipril veya salin verildi. Arteriyel kan basıncı karotis arter kanülasyonu ile verifiye edildi. Deney sonunda ratların testis ağırlıkları, testis histopatolojik skorlaması, sperm sayısı, sperm motilitesi, sperm morfolojisi ve serum testosteron düzeylerini içeren erkek fertilite parametreleri analiz edildi.
Bulgular: Sakubitril/valsartan veya ramipril tedavileri, sperm üretimi, testis morfolojisi ve serum testosteron düzeylerinin radyoimmünoassay incelemesinde kontrol grubuna göre anlamlı bir farklılık göstermedi. Bununla birlikte, sperm motilitesi, RAS inhibisyonu altındaki ratlarda anlamlı olarak azaldı.
Sonuç: Bu bulguya rat sperm kuyruklarındaki anjiyotensin reseptörleri varlığının sebep olması muhtemeldir, çünkü anjiyotensin reseptörleri sperm motilitesinin modülasyonunda rol oynayabilmektedir. Sperm motilitesinde rol oynayan RAS ile ilişkili proteinlerin tanımlanması, motilitedeki rollerini açıklamaya yardımcı olabilir. Verilerimiz, paternal sakubitril / valsartan ve ramipril maruziyetinin erkeklerde fertilizasyonda genel olarak güvenli olduğunu kanıtlamaktadır. (NCI-2019-0233.R1)

Anahtar Kelimeler: Paternal Maruziyet, sakubitril-valsartan; ramipril; spermatozoa

Duygun Altıntaş Aykan, Asli Yaylali, Nadire Eser, Muhammed Seyithanoğlu, Selma Yaman, Ahmet Aykan. The effects of sacubitril/valsartan and ramipril on the male fertility in hypertensive rats. North Clin Istanb. 2020; 7(5): 425-432

Corresponding Author: Duygun Altıntaş Aykan
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