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

Area of Science:

• Nephrology
• Cardiovascular Research
• Pharmacology

Background:

• Chronic kidney disease (CKD) is associated with significant vascular dysfunctions, including endothelial dysfunction and vascular calcification (VC).
• These vascular complications contribute to the high morbidity and mortality in CKD patients.
• Understanding protective mechanisms against these dysfunctions is crucial for therapeutic development.

Purpose of the Study:

• To investigate the potential protective effects of nicorandil, a potassium channel opener, on renal and vascular impairments in a rat model of adenine-induced nephropathy.
• To elucidate the underlying mechanisms of nicorandil's action in this model.

Main Methods:

• A rat model of adenine-induced nephropathy was established.
• Thirty-four rats were divided into Control, Adenine, and Nicorandil (adenine + nicorandil) groups.
• Key biochemical parameters, blood pressure, heart rate, gene expression (eNOS, Nrf2), and aortic vascular calcification were assessed.

Main Results:

• Adenine-induced nephropathy resulted in increased blood pressure, serum creatinine, BUN, plasma renin activity, urinary albumin excretion, and vascular calcification.
• Adenine exposure led to reduced body weight, heart rate, serum calcium, and decreased expression of eNOS and Nrf2 mRNA in aortic tissues.
• Nicorandil treatment significantly improved these parameters, attenuating vascular calcification and enhancing eNOS and Nrf2 gene expression.

Conclusions:

• Nicorandil exhibits a protective effect against vascular and renal impairment in adenine-induced nephropathy in rats.
• This protective effect may be attributed to the attenuation of vascular calcification and the activation of Nrf2 and eNOS pathways in aortic tissues.
• Nicorandil shows promise as a therapeutic agent for managing vascular complications in CKD.