Vasorelaxant Effect of Metformin in Human Umbilical Artery In Vitro

Abstract

Objective: To evaluate the effect of metformin on the vasomotion of human umbilical artery (HUA) in vitro.
Study Design: Experimental study (Ex-vivo Pharmacodynamic study).
Place and Duration of the Study: Department of Pharmacology of Azra Naheed Medical College - Superior University, and Combined Military Hospital, Lahore from Nov 13, 2024 to Apr 30, 2025.
Materials and Methods: A total of 24 HUA samples were obtained from 24 different donors to ensure biological independence, and were divided into 4 groups with a sample size of 6 in each. Fresh HUA tissues with intactendothelium, and without endothelium were suspended in Kreb's solution, pH 7.4. A force transducer (MLT0420) connected with an amplifier (AD Instruments Bridge Amps) was used to record isometric tension.
The vasorelaxant responses of HUA to metformin (1-20 μM/l) were noted. In another setup the responses of metformin in KCl (60μM) precontracted HUA rings were recorded. The response of KCl + PGE were taken as 2 standard.
Results: The effect of metformin (1-20 μM/l) on HUA with intact endothelium showed significant relaxation (p<0.0001) IC was 7.031. The HUA ring with intact endothelium presented with better relaxation than rings 50 without endothelium. The IC were 7.031 and 0.6821 respectively. In case of KCl (60μM) pretreated HUA rings, 50 the findings of metformin and PGE were comparable showing IC 5.739 and 6.248 respectively. 2 50
Conclusion: Metformin with KCl exhibited the strongest vasorelaxation followed by PGE . Metformin alone 2 without endothelium had comparatively weaker relaxation. These findings highlight the significant efficacy of metformin under vasoconstrictive stress. It has potential to protect fetoplacental circulation during GDM pregnancies.