Effects of AT1 Receptor Blockade on Plasma Thromboxane A2 (TXA2) Level and Skin Microcirculation in Young Healthy Women on Low Salt Diet

Abstract

Objective: To determine the effect of AT1 receptor antagonism on skin microcirculation and plasma level of thromboxane A₂ (TXA₂). Methods: Healthy women (n=20) maintained 7 days low salt (LS) diet (intake <40 mmol Na/day) without (LS) or together with 50 mg/per day of losartan (a selective AT1 receptor inhibitor) (LS diet+losartan group). Laser Doppler flowmetry (LDF) measurements of changes in post occlusive hyperemic blood flow, plasma concentration of stable TXA₂ metabolite thromboxane B₂ (TXB₂) and plasma renin activity (PRA) aldosterone concentration, electrolytes (Na⁺, K⁺), as well as blood pressure and heart rate were determined before and after study protocols. Results: PRA and aldosterone increased significantly after 7 days of both LS diet and LS diet+losartan. LS diet or LS diet+losartan administrations had no significant effect on post-occlusion hyperemia While there was no change in TXB₂ after LS diet TXB₂ significantly increased after one week of LS+losartan compared to control levels (cTXB2 pg/mL control 101±80 vs. LS diet+losartan 190±116, p<0.05). Conclusion: These data suggest that inhibition of AT1 receptors could lead to activation of AT2 receptors, which maintain hyperemia, despite the increased level of vasoconstrictor TXA₂. These findings also suggest an important role of crosstalk between renin-angiotensin system (RAS) and arachidonic acid metabolites in the regulation of microcirculation under physiological conditions.