Naringenin antihypertensive power is mediated via abrogation of mineralocorticoid receptor (MCR)/ angiotensin converting enzyme (ACE)/ kidney injury molecule (Kim‐1) signaling pathway

Abstract

Hypertension is a condition with chronic elevation of blood pressure and a common preventable risk factor for cardiovascular disease with attendant global morbidity and mortality. The present study investigated the novel antihypertensive action of Naringenin on NƱ‐Nitro‐L‐arginine Methyl Ester (L‐NAME)‐induced hypertension together with possible molecular mechanism of action. Rats were divided into four groups. Rats in Group A were normotensive. The hypertensive group (Group B) received 40 mg/kg) of L‐NAME alone while Groups C and D were concurrently administered Naringenin (50 mg/kg) or Lisinopril (10 mg/Kg) together with L‐NAME orally for 3 weeks. Blood pressure parameters, markers of oxidative stress and renal damage were measured. The immunohistochemistry of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme were also determined. Results indicated significant increase in oxidative stress markers and decrease in serum nitric oxide bioavailability in hypertensive rats. Furthermore, there were significant increases in serum myeloperoxidase activity, urinary creatinine, albumin, and blood urea nitrogen levels in hypertensive rats in comparison to hypertensive rats treated with Naringenin. Immunohistochemistry revealed higher expression of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme in hypertensive rats. However, co‐treatment with Naringenin mitigated renal oxidative stress, normalized blood pressure and lowered the expression of kidney injury molecule 1, mineralocorticoid receptor, and angiotensin converting enzyme. Combining all, Naringenin offered a novel antihypertensive action through the down regulation of kidney injury molecule 1, deactivation of mineralocorticoid receptor and inhibition of angiotensin converting enzyme.