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

Abstract

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.

Folic acid‐induced animal model of kidney disease

“…[12][13][14][15][16][17][18][19] There are numerous animal models that have been used to elucidate the pathological mechanisms of kidney disease. [19][20][21] Those induced by ischemia, 14,22,23 lipopolysaccharide, [24][25][26][27] cisplatin, [28][29][30] arsenic, [31][32][33] adenine, [34][35][36] cadmium 15,[37][38][39][40] and diabetes [41][42][43][44][45][46] are widely used as animal models of kidney disease. These models have also been used to test the therapeutic effect of a given drug or compound.…”

Nicorandil Decreases Renal Injury in Patients With Coronary Heart Disease Complicated With Type I Cardiorenal Syndrome

“…16,23 Clinical practices have indicated that nicorandil can dilate coronary vessels, increase coronary blood flow, and relieve coronary vasospasm without affecting heart rate, myocardial contractility, myocardial oxygen consumption, or atrioventricular conduction time. [16][17][18][19][20][21][22] Nicorandil is recommended for all types of angina pectoris, especially for spastic angina pectoris. Studies have also confirmed that nicorandil can significantly reduce the incidence of cardiovascular events associated with CHD and improve the prognosis.…”

“…In addition to improving heart function, nicorandil was reported to provide additional renal protection for CKD and reduce the incidence of contrast-induced nephropathy in patients undergoing coronary angiography or interventional therapy. 10,17 Therefore, we investigated the effect of nicorandil on renal function and renal injury in patients with type 1 CRS. We found that both conventional standard treatment and additional nicorandil treatment could improve traditional renal function indexes (Scr and Cys-C).…”

“…15 In addition, some studies have found that nicorandil can provide additional renal protection for chronic kidney disease or significantly reduce the incidence of contrast-induced nephropathy in patients undergoing coronary angiography or percutaneous coronary intervention. 16 The possible mechanism of nicorandil is the reduction of vascular and renal dysfunction 17 or the neutralization of nephrotoxicity by normalizing the TLR4/MAPK P38/NFκ-B inflammatory cascade. 18 Moreover, oral nicorandil reduced cardiac death in hemodialysis patients undergoing coronary revascularization.…”

Harmful and Beneficial Role of ROS 2020

“…reports that pretreatment with nicorandil (K ATP channel opener) causes upregulation of Nrf2 mRNA in the aortic tissues of rats fed with an adenine-rich diet, suggesting that the improvement of oxidative stress in the aortic tissue could reduce the CDK-associated aortic calcifications [5].…”