Time-Dependent Effects of Low-Dose Aspirin on Plasma Renin Activity, Aldosterone, Cortisol, and Catecholamines

Abstract

Abstract-Studies have shown that aspirin may decrease blood pressure when given at bedtime but not when administered on awakening. However, until now, a biologically plausible mechanism of this striking phenomenon was not revealed. We investigated the effect of 100 mg of aspirin administered at bedtime compared with administration on awakening on plasma renin activity and aldosterone levels over 24 hours and excretion of cortisol and catecholamines in 24-hour urine samples. A randomized, placebo-controlled, double-blind, crossover trial was performed in 16 grade 1 hypertensive subjects. During 2 periods of 2 weeks separated by a 4-week washout period, participants used aspirin both at morning and at night, which was blinded with placebo. After both periods, subjects were admitted for 24 hours to measure the aforementioned parameters. Aspirin intake at bedtime compared with on awakening reduced average (24-hour) plasma renin activity by 0.08 g/L per hour (95% CI: 0.03 to 0.13 g/L per hour; Pϭ0.003) without affecting aldosterone levels (95% CI: Ϫ0.01 to 0.01 nmol/L; Pϭ0.93). Cortisol excretion in 24-hour urine was 52 nmol/24 hours (95% CI: 5 to 99 nmol/24 hours; Pϭ0.05) lower, and dopamine and norepinephrine excretions were 0.25 mol/24 hours (95% CI: 0.01 to 0.48 mol/24 hours; Pϭ0.04) and 0.22 mol/24 hours (95% CI: Ϫ0.03 to 0.46 mol/24 hours; Pϭ0.02) lower in patients treated with bedtime aspirin. In conclusion, aspirin taken at bedtime compared with on awakening significantly diminished 24-hour plasma renin activity and excretion of cortisol, dopamine, and norepinephrine in 24-hour urine. Decreased activity of these pressor systems forms a biologically plausible explanation for the finding that aspirin at night may reduce blood pressure, whereas aspirin at morning does not.

Biological Rhythms and Preeclampsia

“…Although not fully understood, this might be related to the circadian secretion pattern of BP regulators. As explored by Snoep et al (2009) aspirin decreases the nocturnal rise in activity of the renin-angiotensin-aldosterone system and in cortisol and catecholamine levels when taken at bedtime, but not in the morning. Another mechanism could involve enhanced release of NO during the night, as exemplified by Hermida et al in a study comparing BP response to aspirin in non-dipper hypertensive patients and dipper patients.…”

“…This action might be linked the antioxidative effect of aspirin, with a reduction in vascular production of superoxide and an increased release of nitric oxide (NO) (Hermida et al, 2005b). Moreover, aspirin has been shown to influence secretion of pressor hormones such as renin, aldosterone, cortisol, and catecholamine (Snoep et al, 2009). Interestingly, this phenomenon seems to be influenced by ingestion time.…”

Sympathetic Nervous System Dysfunction in Multiple Sclerosis, Linking Neurodegeneration to a Reduced Response to Therapy

“…The common use of aspirin in MS patients ( Table 1) is partly attributed to the high prevalence of antiphospholipid antibodies, often present in these patients [78]. The administration of 100 mg aspirin to antihypertensive subjects reduces both BP and NE excretion in urine [79]. Similar results were observed with the administration of 500 mg of aspirin to healthy volunteers [80].…”

The Effects of Different Aspirin Dosing Frequencies and the Timing of Aspirin Intake in Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review

“…The search strategy identified 4,272 records; 28 studies were eligible for inclusion and informed the analysis (see Figure ). Twelve studies investigated the effects of aspirin when administrated once‐daily in the morning / after awakening vs. in the evening / at bedtime; 12 studies compared aspirin administration once‐daily with two or more times daily; and four studies compared once‐daily vs. alternate‐day (or less frequent) aspirin dosing. Table shows the main study characteristics.…”

“…In 9/12 studies, 24‐hour or 48‐hour mean ambulatory blood pressure measurements (ABPM) were reported . Of those, four parallel RCTs conducted by the same research group favored aspirin administration in the evening, with most results being statistically significant (see Figure ).…”