Citrulline Supplementation Improves Aortic Vasodilation and Prevents Aortic Thickening Only in Female Rats
In brief
Citrulline raised aortic relaxation from 42% to 55% in female rats
In this 12-week study of adult rats, citrulline improved aortic relaxation in females, while treated males showed no benefit. Female rats also had less elastic-fiber disruption and a thinner inner aortic layer, but these animal findings do not establish benefit in people; whether sex or hormonal status shapes any human response remains unknown.
- Journal
- Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists (Q1)
- Published
- 30 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Katia Martinez-Gonzalez, Patricia Campos-Bedolla, Claudia Patlán-Lozano, Eduardo Almeida-Gutierrez, Leonor Serrano-Cuevas, Alam Palma-Guzman, et al.
- PMID
- 42958992
- DOI
- 10.1177/15266028261494959
Why clinicians should know about it
- Picked for Histology (top studies of the week, 1 November 2026): Histological analyses showed elastic fiber preservation in treated females
Abstract
BACKGROUND: Aging is associated with endothelial dysfunction and vascular remodeling, partly due to reduced nitric oxide (NO) bioavailability. l-citrulline, a precursor of l-arginine and NO synthesis, has been proposed as a therapeutic strategy to improve vascular function. This study evaluated the effects of chronic citrulline supplementation on aortic structure and vasodilatory function in adult male and female rats. METHODS: Eight-month-old male and female Sprague-Dawley rats were randomly assigned to control or treatment groups. The treated animals received oral malate citrulline (1 g/kg/d) for 12 weeks. We isolated thoracic aortas for histological and morphometric analyses, including tunica media thickness and intima/media ratio. We assessed vascular reactivity in vitro using isolated aortic rings in an organ bath system, measuring acetylcholine (ACh)-induced relaxation following phenylephrine-induced contraction. RESULTS: Citrulline supplementation significantly improved ACh-induced vasorelaxation in female rats compared with female controls (55.14% ± 4.8% vs 42.4% ± 4.3%, P < .05. No differences in vasorelaxation were observed in males between the treated and control groups. Histological analyses showed that treated females had less disruption of elastic fibers and a thinner minimal intima than controls, whereas males showed no structural differences. CONCLUSIONS: Citrulline supplementation improves endothelium-dependent vasodilation and may preserve aortic structural integrity in female rats but not in males. These findings suggest a sex-dependent vascular response to citrulline, potentially mediated by differences in NO signaling and hormonal regulation. Citrulline may represent a therapeutic strategy to improve vascular function during aging, particularly in females. CLINICAL IMPACT: The findings may guide clinical trials investigating how hormonal status and nitric oxide signaling affect the efficacy of citrulline supplementation in female patients. Ultimately, these insights could establish citrulline as a targeted, preventive intervention to preserve aortic structural integrity and reduce cardiovascular disease risk in the aging female population.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.