Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide

Abstract

Background: While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking.

Objectives: We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms.

Methods: We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger).

Results: Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01).

Conclusions: These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555.

Keywords: cheese; dairy; endothelial function; nitric oxide; older adults; oxidative stress; sodium; superoxide; vasodilation.

FIGURE 1

CVC (% maximum) in response to perfusion of exogenous ACh (A) alone and (B) with concurrent perfusion of the NO synthase inhibitor, N^G-nitro-L-arginine methyl ester, in healthy, older adults who consumed 4 separate 8-d diets varying in sodium content and source. Values are means ± SEMs, n = 11. *P < 0.05, HNa versus LNa; ^†P < 0.05, HNa versus LNaC; ^‡P < 0.05, HNa versus HNaC. ACh, acetylcholine; CVC, cutaneous vascular conductance; HNa, high-sodium diet; HNaC, high-sodium, high-cheese diet; LNa, low-sodium diet; LNaC, low-sodium, high-cheese diet.

FIGURE 2

CVC (% maximum) in response to perfusion of exogenous ACh alone and with concurrent perfusion of ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibition], or tempol (superoxide scavenger) in healthy, older adults who consumed the following 8-d diets: (A) LNa, (B) LNaC, (C) HNa, or (D) HNaC. Values are means ± SEMs, n = 11. *P < 0.05, Ringer's versus ascorbate; ^†P < 0.05, Ringer's versus apocynin; ^‡P < 0.05, Ringer's versus tempol. ACh, acetylcholine; CVC, cutaneous vascular conductance; HNa, high-sodium diet; HNaC, high-sodium, high-cheese diet; LNa, low-sodium diet; LNaC, low-sodium, high-cheese diet.