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N‐Acetylcysteine Attenuates Aldosterone induced Vasoconstriction in Individuals with Type 2 Diabetes
Author(s) -
Finsen Stine Louise Hoyer,
Mortensen Stefan
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05400
Subject(s) - aldosterone , medicine , blood pressure , vasoconstriction , endocrinology , hemodynamics , type 2 diabetes , vasodilation , population , diabetes mellitus , environmental health
Individuals with type 2 diabetes (T2D) have a high risk of developing cardiovascular disease. Chronic elevation of plasma aldosterone could contribute to endothelial dysfunction within this population by ROS dependent mechanisms. The antioxidant N ‐acetylcysteine (NAC) is known for its free radical scavenging properties and NAC may potentiate the activity of nitric oxide (NO) directly by increasing NO‐bioavailability. A shift in the balance between vasoconstrictor and vasodilator responses to aldosterone could be involved in the detrimental actions of aldosterone, and NAC could revoke this effect. The purpose of this study was to investigate if infusion of NAC would improve the vascular response to infused aldosterone in individuals with T2D. Methods In 13 subjects with T2D and 14 control subjects (matched on age and activity level), we measured leg hemodynamics during 10 min of incremental doses of infused aldosterone (0.2 and 5 ng/min/L leg volume) into the femoral artery, with and without co‐infusion of NAC (125 mg/kg/hour for 20 min; 25 mg/kg/hour (maintenance dose)). Leg blood flow (LBF; ultrasound Doppler) and arterial blood pressure was measured, and femoral arterial and venous blood samples were collected. Data was analyzed with one‐way repeated measure ANOVA (within groups) and two‐way ANOVA (between groups). Results LBF and leg vascular conductance (LVC) decreased during infusion of aldosterone at the high dose ( p <0.05) in the individuals with T2D, whereas co‐infusion of NAC attenuated this response. In the control group, there was no change in LBF and LVC during aldosterone infusion independently of NAC infusion. In both groups, venous aldosterone levels increased during aldosterone infusion ( p <0.05), and there was no difference between groups in aldosterone concentrations at baseline or during infusions. Conclusion These results indicate that T2D is associated with a vasoconstrictor response to physiological levels of infused aldosterone and an increase in NO‐bioavailability attenuates this effect. Support or Funding Information Supported by the Independent Research Fund, Denmark and Region of Southern Denmark