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Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate.

Translational research : the journal of laboratory and clinical medicine (2013-10-12)
Shao-Ju Chien, Kuan-Miao Lin, Hsuan-Chang Kuo, Chien-Fu Huang, Ying-Jui Lin, Li-Tung Huang, You-Lin Tain
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium nitrate, ACS reagent, ≥99.0%
Sigma-Aldrich
L-Citrulline, ≥98% (TLC)
Sigma-Aldrich
Sodium nitrate, ≥99.0%, suitable for plant cell culture
Sigma-Aldrich
Sodium nitrate, BioXtra, ≥99.0%
Sigma-Aldrich
Sodium nitrate, 99.995% trace metals basis
Sigma-Aldrich
Sodium nitrate, BioUltra, ≥99.0% (T)
Sigma-Aldrich
Sodium nitrate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%