Dietary Salt and Microvascular Function

Influence of High Salt Diet on Microvascular Reactivity in Young Healthy Subjects

It is well accepted that high-salt (HS) intake is an essential risk factor in development and progression of hypertension. Results of some recent studies suggest that some of the deleterious effects of a HS diet are independent of elevated blood pressure (BP) and may occur in normotensive individuals and are associated with impaired endothelial function. However, the effects of acute salt loading on endothelial function and vascular reactivity in young healthy individuals are still scarce and inconsistent.

The purpose of present study is to determine whether one week of HS intake affects microvascular reactivity in young healthy subjects without changes in BP. In addition, the investigators sought to evaluate if potential HS diet-induced microvascular dysfunction is associated with changes in oxidative stress level and/or with modification of immunological response in young healthy subjects.

Study Overview

• Status: Unknown
• Conditions: Salt; Excess
• Intervention / Treatment: Other: Low Salt (LS) diet; Other: High Salt (HS) diet

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ana - Stupin, MD, PhD; Phone Number: +385915134958; Email: anacavka@mefos.hr
• Study Contact Backup: Name: Ines - Drenjancevic, MD, PhD; Phone Number: +385912241406; Email: ines.drenjancevic@mefos.hr

Study Locations

• Croatia
  • Osijek, Croatia, 31000
    • Recruiting
    • Faculty of Medicine Osijek, Laboratory for Clinical and Sport Physiology
    • Contact: Ana Stupin, MD, PhD; Phone Number: '385915134598; Email: anacavka@mefos.hr
    • Contact: Ines Drenjancevic, MD, PhD; Phone Number: '385912241406; Email: ines.drenjancevic@mefos.hr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- healthy volunteers

Exclusion Criteria:

• oral contraceptives
• drugs that could affect the endothelium
• hypertension
• coronary artery disease
• diabetes
• hyperlipidaemia
• renal impairment
• cerebrovascular and peripheral artery disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low salt diet; All subjects will be instructed to maintain a low-sodium (LS) diet, with an intake of less than 2.3 g of salt per day (DASH eating plan; US Department of Health and Human Services, 2006) for 7 days (washout period).	Other: Low Salt (LS) diet; Intake of less than 2.3 g of salt per day for 7 days.
Experimental: high salt diet; After washout period, all subjects will be instructed to maintain a high-sodium (HS) diet, with an intake of 11.2 g of salt per day for 7 days.	Other: High Salt (HS) diet; Intake of 11.2 g of salt per day for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
microvascular reactivity	Cutaneous microvascular blood flow will be measured by Laser Doppler Flowmetry in response to vascular occlusion (post occlusive reactive hyperemia- PORH) and in response to iontophoresis of acetylcholine (ACh) (endothelium dependent vasodilation) before and after diet protocols.	two weeks after starting the protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
oxidative stress	As direct indicator of oxidative stress, byproducts of lipid peroxidation - TBARS method (Thiobarbituric Acid Reactive Substances) with malondialdehyde (MDA) as standard (µM MDA) will be measured before and after LS and HS diet protocol (spectrophotometric method).	two weeks after starting the protocol
modification of immunological response by high salt diet	Activated monocytes/macrophages and neutrophils will be measured by flow cytometry, with distinction of subpopulation of monocytes/macrophages (classical/nonclassical), their activation and the expression of the integrin LFA-1 (lymphocyte function-associated antigen 1) and VLA-4 (Very Late Antigen-4) - ligands VCAM-1 (vascular cell adhesion molecule 1 ) and ICAM-1 (vascular cell adhesion molecule 1).	two weeks after starting the protocol
antioxidant capacity	As an indicator of antioxidant capacity, the ferric reducing ability of plasma - the FRAP assay (Ferric reducing ability of plasma) with Trolox used as standard (mM Trolox) will be measured before and after LS and HS diet protocol (spectrophotometric method).	two weeks after starting the protocol

Collaborators and Investigators

• Sponsor: Josip Juraj Strossmayer University of Osijek
• Investigators: Principal Investigator: Ines Drenjancevic, MD, PhD, Faculty of Medicine, University of Osijek, Croatia

Publications and helpful links

General Publications

• Cavka A, Cosic A, Jukic I, Jelakovic B, Lombard JH, Phillips SA, Seric V, Mihaljevic I, Drenjancevic I. The role of cyclo-oxygenase-1 in high-salt diet-induced microvascular dysfunction in humans. J Physiol. 2015 Dec 15;593(24):5313-24. doi: 10.1113/JP271631. Epub 2015 Dec 7.
• Cavka A, Jukic I, Ali M, Goslawski M, Bian JT, Wang E, Drenjancevic I, Phillips SA. Short-term high salt intake reduces brachial artery and microvascular function in the absence of changes in blood pressure. J Hypertens. 2016 Apr;34(4):676-84. doi: 10.1097/HJH.0000000000000852.
• Cavka A, Cosic A, Grizelj I, Koller A, Jelakovic B, Lombard JH, Phillips SA, Drenjancevic I. Effects of AT1 receptor blockade on plasma thromboxane A2 (TXA2) level and skin microcirculation in young healthy women on low salt diet. Kidney Blood Press Res. 2013;37(4-5):432-42. doi: 10.1159/000355723. Epub 2013 Oct 13.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): May 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: March 15, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (Estimate): April 4, 2016

Study Record Updates

• Last Update Posted (Estimate): April 5, 2016
• Last Update Submitted That Met QC Criteria: April 3, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: microvascular function; laser Doppler flowmetry; high salt diet
• Other Study ID Numbers: 215861071012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No