Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate
Abstract
Nitric oxide (NO) deficiency mediates oxidative stress in the kidney and is involved in the development of hypertension. NO synthesis occurs via 2 pathways: nitric oxide synthase (NOS) dependent and NOS-independent. We tested whether the development of hypertension is prevented by restoration of NO by dietary l-citrulline or nitrate supplementation in young spontaneously hypertensive rats (SHRs). Male SHRs and normotensive Wistar Kyoto control rats (WKYs)s age 4 weeks were assigned to 4 groups: untreated SHRs and WKYs, and SHRs and WKYs that received 0.25% l-citrulline for 8 weeks. In our second series of studies, we replaced l-citrulline with 1 mmol/kg/d sodium nitrate. All rats were sacrificed at age 12 weeks. We found an increase in the blood pressure of SHRs was prevented by dietary supplementation of l-citrulline or nitrate. Both treatments restored NO bioavailability and reduced oxidative stress in SHR kidneys. l-Citrulline therapy reduced levels of l-arginine and asymmetric dimethylarginine (ADMA)-an endogenous inhibitor of NOS-and increased the l-arginine-to-ADMA ratio in SHR kidneys. Nitrate treatment reduced plasma levels of l-arginine and ADMA concurrently in SHRs. Our findings suggest that both NOS-dependent and -independent approaches in the prehypertensive stage toward augmentation of NO can prevent the development of hypertension in young SHRs.
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Previous experiments demonstrated that both nitrate and citrulline supplementation induced acute vasodilatation in rodents.
“Previous experiments demonstrated that both nitrate and citrulline supplementation induced acute vasodilatation in rodents (Chien et al. 2014)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Chien et al. 2014
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- Authors
- Chien, S.-J., Lin, K.-M., Kuo, H.-C., Huang, C.-F., Lin, Y.-J., Huang, L.-T., & Tain, Y.-L.
- Affiliations
- Chang Gung University (TW)
- Corresponding author
- Tain, You-Lin
- Venue
- Translational Research
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 163
- Issue
- 1
- Pages
- 43-52
- ISSN
- 1878-1810 (ISSN-L)
- 1931-5244
- OpenAlex
- W1999375228
- Cited by
- 61
- References
- 23
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 4 · 2014: 6
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Translational research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- nitric oxide, hypertension prevention, spontaneously hypertensive rats, citrulline, sodium nitrate, dietary supplementation, oxidative stress, kidney, asymmetric dimethylarginine, L-arginine, nitric oxide synthase, NO bioavailability
- MeSH terms
- Animals, Arginine, Citrulline, Hypertension, Male, Nitrates, Nitric Oxide, Rats, Inbred SHR, Rats, Inbred WKY, Dietary Supplements, Rats
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