L-arginine and lisinopril supplementation protects against sodium fluoride–induced nephrotoxicity and hypertension by suppressing mineralocorticoid receptor and angiotensin-converting enzyme 3 activity

Abstract

Sodium uoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil and the atmosphere.The persistent and alarming rate of increase in cardiovascular and renal diseases and disorders caused by chemicals such as sodium uoride (NaF) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the renoprotective and antihypertensive effects of L-Arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into ve groups of six rats each as Control, NaF (300 ppm), NaF + L-Arginine (100 mg/kg), NaF + L-Arginine (200 mg/kg), and NaF + Lisinopril (10 mg/kg), respectively; orally for eight days. Histopathological examination and immunohistochemistry of renal angiotensin converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defence system, and blood pressure parameters were determined. L-Arginine and Lisinopril signi cantly (p < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic and mean arterial blood pressure of the treated groups were signi cantly (p < 0.05) reduced compared with the hypertensive group. This nding was concurrent with signi cantly increased serum bioavailability of nitric oxide in the hypertensive treated with and Lisinopril. Also, there was signi cant reduction in the level of blood urea nitrogen and creatinine in the serum of the hypertensive rats treated with L-arginine and Lisinopril. There was signi cant (p < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L arginine and Lisinopril. The results of this study suggest that L-Arginine and and Lisinopril normalized high blood pressure, reduced oxidative stress, reduced the expression of renal angiotensin converting enzyme and mineralocorticoid receptor and improved nitric oxide production. Thus, L-Arginine holds promise as a potential therapy against hypertension and renal damage.

Causal association between blood metabolites and risk of hypertension: a Mendelian randomization study

“…Many studies have found a close relationship between arginine and hypertension. In patients with hypertension, the levels of arginine were low (42), and arginine supplementation could lower blood pressure levels (43)(44)(45)(46). Arginine synthesizes nitric oxide by nitric oxide synthase, and nitric oxide plays a vital role as an intercellular messenger and neurotransmitter in the cardiovascular system and nervous system, including promoting vasodilation, inhibiting platelet aggregation, inhibiting smooth muscle cell proliferation and so on (47).…”

Datasheet1.docx

“…Many studies have found a close relationship between arginine and hypertension. In patients with hypertension, the levels of arginine were low (42), and arginine supplementation could lower blood pressure levels (43)(44)(45)(46). Arginine synthesizes nitric oxide by nitric oxide synthase, and nitric oxide plays a vital role as an intercellular messenger and neurotransmitter in the cardiovascular system and nervous system, including promoting vasodilation, inhibiting platelet aggregation, inhibiting smooth muscle cell proliferation and so on (47).…”