Key result
GSNO-loaded nanoparticles and DETA NONOate prevent kidney dysfunction and hypertension in rats with CKD.
Why the study?
Hypertension is poorly controlled in pediatric CKD, where NO deficiency plays a pivotal role, but NO has a short half-life and lacks targeted delivery.
Does NO delivery via GSNO-loaded nanoparticles or DETA NONOate prevent hypertension and kidney dysfunction in a young rat model of adenine-induced CKD?
Does NO delivery via GSNO-loaded nanoparticles or DETA NONOate prevent hypertension and kidney dysfunction in a young rat model of adenine-induced CKD?
Targeted NO delivery using GSNO-loaded nanoparticles effectively prevents hypertension and kidney dysfunction in a pediatric rat model of CKD.
Preclinical only; extends targeted NO delivery research in pediatric CKD models but should not yet change practice.
Hypertension is the most common complication of chronic kidney disease (CKD) in children but is still poorly controlled. Nitric oxide (NO) deficiency plays a pivotal role in CKD and hypertension. NO is known to have health benefits, while NO typically has a short half-life and is not specifically targeted. In this study, we used a pediatric CKD model, which was induced in young rats by feeding them 0.25% adenine. We investigated two different NO donors, namely S-nitrosoglutathione (GSNO) and diethylenetriamine/NO adduct (DETA NONOate) via intraperitoneal injection at 10 mg/kg/day daily for 3 weeks. GSNO was delivered by Cu2+-doped zeolitic imidazolate framework (Cu/ZIF-8) nanoparticles to generate NO. As a result, we observed Cu/ZIF-8 nanoparticles were successfully loaded with GSNO and were able to release NO. Young rats fed with adenine displayed kidney dysfunction and hypertension at 9 weeks of age, which were prevented by GSNO-loaded nanoparticle or DETA NONOate treatment. GSNO-loaded nanoparticles reduced CKD-induced hypertension, which was related to an enhanced endogenous NO-generating system, reduced renal oxidative stress, and downregulated several components belonging to the classic renin–angiotensin (RAS) system. Our results cast new light on targeting NO delivery through the use of nanoparticles aiming to improve child-focused outcomes related to CKD worthy of clinical translation.
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Tain et al. (2023) studied Chronic Kidney Disease and hypertension. GSNO-loaded Cu/ZIF-8 nanoparticles or DETA NONOate was evaluated on Kidney dysfunction and hypertension. GSNO-loaded nanoparticles and DETA NONOate prevented kidney dysfunction and hypertension in young rats with adenine-induced chronic kidney disease.
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