Citrulline Supplementation Improves Aortic Vasodilation and Prevents Aortic Thickening Only in Female Rats.

Authors

Katia Martinez-Gonzalez, Patricia Campos-Bedolla, Claudia Patlán-Lozano, Eduardo Almeida-Gutierrez, Leonor Serrano-Cuevas, Alam Palma-Guzman, Octavio Arellano-Escudero, Paola Garcia-delaTorre

Published in

Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists. Pages 15266028261494959. Oct 30, 2026. Epub Oct 30, 2026.

Abstract

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.
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.
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.
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.
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.

PMID:
42958992
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.

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