title: Dietary nitrate improves cardiac contractility via enhanced cellular Ca²⁺ signaling.
abstract: The inorganic anion nitrate (NO3 (-)), which is naturally enriched in certain vegetables (e.g., spinach and beetroot), has emerged as a dietary component that can regulate diverse bodily functions, including blood pressure, mitochondrial efficiency, and skeletal muscle force. It is not known if dietary nitrate improves cardiac contractility. To test this, mice were supplemented for 1-2 weeks with sodium nitrate in the drinking water at a dose similar to a green diet. The hearts from nitrate-treated mice showed increased left ventricular pressure and peak rate of pressure development as measured with the Langendorff heart technique. Cardiomyocytes from hearts of nitrate-treated and control animals were incubated with the fluorescent indicator Fluo-3 to measure cytoplasmic free [Ca(2+)] and fractional shortening. Cardiomyocytes from nitrate-treated mice displayed increased fractional shortening, which was linked to larger Ca(2+) transients. Moreover, nitrate hearts displayed increased protein expression of the L-type Ca(2+) channel/dihydropyridine receptor and peak L-type Ca(2+) channel currents. The nitrate-treated hearts displayed increased concentration of cAMP but unchanged levels of cGMP compared with controls. These findings provide the first evidence that dietary nitrate can affect the expression of important Ca(2+) handling proteins in the heart, resulting in increased cardiomyocyte Ca(2+) signaling and improved left ventricular contractile function. Our observation shows that dietary nitrate impacts cardiac function and adds understanding to inorganic nitrate as a physiological modulator.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Pironti
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Ivarsson
authors.affiliation: Unit of Cardiology, Department of Medicine Solna, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Alex Bersellini
authors.initials: AB
authors.lastname: Farinotti
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: William
authors.initials: W
authors.lastname: Jonsson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Shi-Jin
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Duygu
authors.initials: D
authors.lastname: Bas
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Camilla I
authors.initials: CI
authors.lastname: Svensson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Westerblad
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Unit of Cardiology, Department of Medicine Solna, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.|Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Pernow
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lanner
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden. daniel.c.andersson@ki.se.|Unit of Cardiology, Department of Medicine Solna, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden. daniel.c.andersson@ki.se.|Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. daniel.c.andersson@ki.se.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Andersson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020013:Calcium Signaling / Q000502:physiology*; D004032:Diet; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D000067268:Isolated Heart Preparation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000494:pharmacology*; D018408:Patch-Clamp Techniques
chemical_list: D009566:Nitrates; C031618:sodium nitrate
keywords: Calcium; Cardiac; Contractility; Diet