Nicorandil suppresses urinary protein excretion and activates eNOS in Dahl salt-sensitive hypertensive rats

Tashiro, Yoshihito; Serizawa, Kenichi; Endo, Koichi

doi:10.1007/s10157-014-0998-6

Cited by 13 publications

(14 citation statements)

References 22 publications

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“…The decrease in the iNOS expression in Group 3 may be due to antioxidant and anti‐inflammatory effects of nicorandil. As stated in the study of Tashiro et al [30], nicorandil increases eNOS expression, and the increase in eNOS activity may also contribute to the renoprotective effect of nicorandil.…”

Section: Discussionmentioning

confidence: 75%

“…The renoprotective effects of nicorandil have been reported in several models, such as renal ischemia–reperfusion, diabetic nephropathy, and remnant kidney [30]. Previous research reported that nicorandil acted as both a nitrovasodilator and potassium channel opener.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, nicorandil was shown to activate cytoplasmic guanylate cyclase, leading to an increase in cellular levels of cyclic guanosine monophosphate, a reduction in cytosolic calcium, and thus the relaxation of vascular smooth muscle [35]. Tashiro et al [30] demonstrated that nicorandil not only increased total eNOS expression but also the state of eNOS coupling in high‐salt‐loaded Dahl salt‐sensitive hypertensive rats. They concluded that the increase in eNOS activity may contribute to the renoprotective effect of nicorandil.…”

Section: Discussionmentioning

confidence: 99%

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Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction

Öztürk

Fırat

Tekçe

et al. 2017

The Kaohsiung J of Med Scie

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To evaluate the effects of nicorandil in a rat kidney model of partial unilateral ureteral obstruction (PUUO). Thirty male rats were randomly divided into three groups as follows: (1) Group 1 (Sham-control), ureters of the rats were manipulated but not ligated; (2) Group 2 (PUUO-untreated), PUUO was performed with two-thirds of the left ureter embedded in the psoas muscle; and (3) Group 3 (PUUO-nicorandil treated). After PUUO was established, nicorandil (15 mg/kg/day) was administered by gastric lavage for 21 days to determine its effects on PUUO-induced histopathological-, functional-, and oxidative stress-induced changes. The serum levels of blood urea nitrogen and creatinine were reduced in Group 3. The level of urinary albumin and the ratio of urinary protein/creatinine were increased in the kidneys of Group 2 but decreased in Group 3. Malondialdehyde value was decreased in Group 3 compared with Group 2. Antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) were decreased in Group 2. Nicorandil treatment caused an increase in these enzyme activities. In Group 3, leukocyte infiltration and tubular dilatation were significantly reduced. Other parameters, such as degeneration of tubular epithelium and fibrosis, also showed a marked improvement in Group 3. Expression of inducible nitric oxide synthase in Group 2 and expression of endothelial nitric oxide synthase in Group 3 were significantly elevated. Nicorandil can inhibit renal tubular damage and tubulointerstitial fibrosis by reducing the effects of oxidative stress after PUUO.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction

Öztürk

Fırat

Tekçe

et al. 2017

The Kaohsiung J of Med Scie

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“…Interestingly, another study showed that in a rat remnant kidney model of chronic kidney disease, treatment with nicorandil preserved renal function by blocking oxidative stress‐related injury of podocytes and macrophages . Moreover, recent evidence from study in Dahl salt‐sensitive hypertensive rats showed that nicorandil prevented the development of renal dysfunction with the suppression of urinary protein excretion and the activation of endothelial nitric oxide synthase . Taken together, nicorandil may protest against the incidence of CIN via various possible mechanisms, and future studies are needed to clarify the exact molecular pathways underlying the preventative efficacy of nicorandil against CIN.…”

Section: Discussionmentioning

confidence: 99%

Nicorandil for the prevention of contrast‐induced nephropathy: A meta‐analysis of randomized controlled trials

Jiao

et al. 2018

Cardiovascular Therapeutics

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“…To the best of our knowledge, this is the first study that examined the role of eNOS as a potential mechanism for the improvement of adenine with nicorandil. However, Date et al (2005), Hongo et al (2005) and Tashiro et al (2015) showed that nicorandil increased endotheliumderived NO production by activation of eNOS, inhibited endothelial cell death, and exerted anti-inflammatory and antioxidative effects and this may contribute to the protective effect of nicorandil.…”

Section: Control Control Adeninementioning

confidence: 98%

Effects of nicorandil on vascular and renal dysfunctions in adenine-induced nephropathy: Possible underlying mechanisms

Hussein

El-Dosoky²,

Malek³

et al. 2019

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Vascular dysfunctions in chronic kidney disease (CKD) include endothelial dysfunctions and vascular calcification (VC). In the present study, we examined the possible protective effect of nicorandil (potassium channel opener) on renal and vascular dysfunctions in a rat model of adenine-induced nephropathy and its underlying mechanisms. Thirty-four male Sprague-Dawley rats were randomly allocated into 3 groups: Control group, Adenine group (animals received high-adenine diet for 4 weeks), and Nicorandil group (animals received adenine for 4 weeks and nicorandil 1 mg/kg per oral for 4 weeks). The results showed significant reduction in the body weight, heart rate (HR), hemoglobin contents, serum Ca 2+ and reduction in the expression of mRNA of endothelial nitric oxide synthase (eNOS) and nuclear factor erythroid related factor 2 (nrf2) genes in aortic tissues with significant increase in arterial blood pressure (ABP), serum creatinine, blood urea nitrogen (BUN), plasma renin activity (PRA), K + and phosphate (PO 4 3-), urinary albumin excretion (UAE) and aortic VC in Adenine group compared to normal group (p < 0.05). On the other hand, coadminsitration of nicorandil caused significant improvement in the studied parameters compared to Adenine group (p < 0.05). We concluded that nicorandil has a potential protective effect against the vascular and renal impairment induced by adenine, which might be due to attenuation of vascular calcifications, activation of Nrf2 and eNOS genes in aortic tissues.

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Nicorandil suppresses urinary protein excretion and activates eNOS in Dahl salt-sensitive hypertensive rats

Abstract: In DS rats fed a HS diet, nicorandil prevented the development of renal dysfunction, which was accompanied by an increase in eNOS expression in the kidneys.

Cited by 13 publications

References 22 publications

Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction

Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction

Nicorandil for the prevention of contrast‐induced nephropathy: A meta‐analysis of randomized controlled trials

Effects of nicorandil on vascular and renal dysfunctions in adenine-induced nephropathy: Possible underlying mechanisms

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