Influence of antihypertensive treatment on RAAS peptides in newly diagnosed hypertensive patients

ABSTRACT

Objective: Recently, the influence of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) gained increasing attention, especially since concerns were raised regarding a potential influence of RAAS inhibitors on Corona Virus Disease 2019 (COVID-19). Our objective was to study the effect of recently initiated antihypertensive drugs on Angiotensin (Ang) II (1-8) and Ang (1-7) as markers of the pro-inflammatory ACE/Ang II/Ang Type 1 receptor (AT1R) axis and the counteractive ACE2/Ang (1-7)/Mas R axis in patients with newly diagnosed hypertension. Design and method: Randomized, open-label trial investigating RAAS peptide profiles after initiation of antihypertensive treatment with either perindopril, olmesartan, amlodipine, or hydrochlorothiazide. Ang II and Ang (1-7) concentrations were measured at 8am and 12am at day of treatment initiation and after four weeks of treatment. Results: 80 patients were randomized in a 1111 fashion. Between the four substances, we found significant differences for the concentrations of Ang II (p<0.0005 for 8 and 12am) and Ang (1-7) (p=0.019 for 8am and <0.0005 for 12am) four weeks after treatment start. Ang II was decreased by perindopril (p=0.002), and increased by olmesartan (p<0.0005) and amlodipine (p=0.012), and hydrochlorothiazide (p=0.001) (Figure panel A). Ang (1-7) was increased by perindopril and olmesartan (p=0.008 and 0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p=0.317 and 0.109) (Figure panel B). Conclusions: Initiation of antihypertensive therapy causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptide shifts upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.