DOI: 10.1177/15266028261494959 ISSN: 1526-6028

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

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

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