Hughan, Kara S.;
Levine, Andrea;
Helbling, Nicole;
Anthony, Steven;
DeLany, James P.;
Stefanovic-Racic, Maja;
Goodpaster, Bret H.;
Gladwin, Mark T.
Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome
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Medientyp:
E-Artikel
Titel:
Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome
Beteiligte:
Hughan, Kara S.;
Levine, Andrea;
Helbling, Nicole;
Anthony, Steven;
DeLany, James P.;
Stefanovic-Racic, Maja;
Goodpaster, Bret H.;
Gladwin, Mark T.
Erschienen in:
Hypertension, 76 (2020) 3, Seite 866-874
Sprache:
Englisch
DOI:
10.1161/hypertensionaha.120.14930
ISSN:
0194-911X;
1524-4563
Entstehung:
Anmerkungen:
Beschreibung:
The nitrate-nitrite-NO pathway regulates NO synthase–independent vasodilation and NO signaling. Ingestion of inorganic nitrite has vasodilatory and blood pressure–lowering effects. Preclinical studies in rodent models suggest there may be a benefit of nitrite in lowering serum triglyceride levels and improving the metabolic syndrome. In a phase 2 study, we evaluated the safety and efficacy of chronic oral nitrite therapy in patients with hypertension and the metabolic syndrome. Twenty adult subjects with stage 1 or 2 hypertension and the metabolic syndrome were enrolled in an open-label safety and efficacy study. The primary efficacy end point was blood pressure reduction; secondary end points included insulin-dependent glucose disposal and endothelial function measured by flow-mediated dilation of the brachial artery and intima-media diameter of the carotid artery. Chronic oral nitrite therapy (40 mg/3× daily) was well tolerated. Oral nitrite significantly lowered systolic, diastolic, and mean arterial pressures, but tolerance was observed after 10 to 12 weeks of therapy. There was significant improvement in the intima-media thickness of the carotid artery and trends toward improvements in flow-mediated dilation of the brachial artery and insulin sensitivity. Chronic oral nitrite therapy is safe in patients with hypertension and the metabolic syndrome. Despite an apparent lack of enzymatic tolerance to nitrite, we observed tolerance after 10 weeks of chronic therapy, which requires additional mechanistic studies and possible therapeutic dose titration in clinical trials. Nitrite may be a safe therapy to concominantly improve multiple features of the metabolic syndrome including hypertension, insulin resistance, and endothelial dysfunction. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01681810.