Physiological Regulation of Endometrial Blood Flow via Nitric Oxide Synthase Pathways in a Sildenafil-Treated Murine Model

International Journal of Anatomy and Physiology | Vol. 15, No. 11, November 2026 | pp. 154–162

DOI: 10.46882/2026/IJAP/001018

Research Article

Title: Physiological Regulation of Endometrial Blood Flow via Nitric Oxide Synthase Pathways in a Sildenafil-Treated Murine Model

Names of Authors: A. L. Vance¹, H. M. El-S基礎²*

Authors’ Affiliations:
¹ Department of Physiology, University of Edinburgh Medical School, Edinburgh, United Kingdom.
² Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Abstract:
Adequate endometrial perfusion is a primary determinant of uterine receptivity and successful embryo implantation. This study investigated the role of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) pathways in regulating uterine microvascular hemodynamics following sildenafil citrate administration. Thirty adult female C57BL/6 mice were randomized into three groups (n = 10): Control (vehicle), Low-Dose Sildenafil (5 mg/kg/day), and High-Dose Sildenafil (20 mg/kg/day), administered intraperitoneally for 7 consecutive days during the peri-implantation phase. Uterine blood flow impedance was monitored using micro-ultrasound Doppler imaging. Endometrial tissue was processed for western blot analysis and immunohistochemical localization of eNOS and iNOS. Sildenafil treatment induced a significant, dose-dependent decrease in the uterine artery pulsatility index (1.12 ± 0.08 in the high-dose group vs. 1.68 ± 0.14 in controls; p < 0.01), indicating decreased vascular resistance. Western blots revealed a significant 2.4-fold up-regulation of eNOS protein expression in endometrial endothelial cells in the high-dose group (p < 0.05), while iNOS expression remained unchanged, avoiding inflammatory cytotoxicity. Immunohistochemistry confirmed dense localization of eNOS along the microvascular endothelium of the functional zone. These results demonstrate that sildenafil improves endometrial perfusion primarily through the up-regulation of the eNOS pathway, enhancing physiological vasodilation without triggering iNOS-mediated inflammatory responses.

Keywords: Endometrial blood flow, eNOS, Sildenafil citrate, Micro-ultrasound, Uterine receptivity.

Manuscript Timeline: Received: August 01, 2026; Revised: September 22, 2026; Accepted: October 10, 2026; Published: November 04, 2026.

Citation: Vance AL, El-S基础 HM. Physiological Regulation of Endometrial Blood Flow via Nitric Oxide Synthase Pathways in a Sildenafil-Treated Murine Model. International Journal of Anatomy and Physiology. 2026; 15(11): 154–162. doi:10.46882/2026/IJAP/001018

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