Beneficial effects of nicotinamide on hypertensive mice with impaired endothelial nitric oxide function.
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ABSTRACT: Nicotinamide (Nam, amide form of niacin acid or nicotinate), a precursor for nicotinamide adenine dinucleotide (NAD+), is important for normal physiological function of organisms. Nam also suppresses mobilization of Ca2+ from sarcoplasmic reticulum into cytoplasm through inhibiting ADP-ribose cyclase. Previously, we have demonstrated that a pharmacological dose of Nam normalizes maternal blood pressure in mouse models of preeclampsia, a pregnancy related hypertensive disorder. We hypothesized that Nam could decrease blood pressure in hypertensive conditions unrelated to pregnancy. Nam at a dose of 500 mg/kg/day was given to wild type (WT) mice treated with L-NAME, endothelial nitric oxide synthase (eNOS)-null and renin transgenic (Renin-Tg) mice via drinking water. Blood pressure was measured by tail-cuff at different stages of treatment. The function and structure of kidneys of WT mice with L-NAME were determined at the end of the study. The gene expression of markers of inflammation and fibrosis in the kidneys of WT mice with L-NAME was also measured. Nam effectively prevented increase in blood pressure in L-NAME treated mice and decreased elevated blood pressure in eNOS-null mice. However, it did not alter high blood pressure in Renin-Tg mice. Nam prevented increase in urinary albumin excretion and collagen deposit in kidneys of WT mice treated with L-NAME. In addition, Nam significantly decreased the mRNA levels of the markers of inflammation and fibrosis in the kidneys of WT mice treated with L-NAME. Nam may execute beneficial effects on hypertensive conditions associated with eNOS dysfunction via suppressing inflammation. Because Nam is generally regarded as safe in humans, it merits further evaluation for the tailored treatment for the subgroup of hypertensive cases associated with impaired eNOS system.
SUBMITTER: Huynh PK
PROVIDER: S-EPMC7470241 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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