Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®

Abstract

Objective:The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS) of hypertensive black and white African men by using RAS equilibrium analysis.Materials and methods:This sub-study involved 23 black (n = 15) and white (n = 8) hypertensive men aged 39.5–41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods.Results:The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005) and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001) encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7) (1.8 and 3.0 pg/ml), were detected in black and white hypertensive men, respectively.Conclusions:The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite.

2020 International Society of Hypertension Global Hypertension Practice Guidelines

“…• Black populations, whether residing in Africa, the Caribbean, United States, or Europe, develop hypertension and associated organ damage at younger ages, have a higher frequency of resistant and nighttime hypertension, and a higher risk of kidney disease, 131 stroke, HF, and mortality, 132 than other ethnic groups. • This increased cardiovascular risk may be due to physiological differences including a suppressed RAAS, 133,134 altered renal sodium handling, 135 increased cardiovascular reactivity, 136 and early vascular aging (large artery stiffness…”

Leptin and its Relation to Autonomic Activity, Endothelial Cell Activation and Blood Pressure in a Young Black and White Population: The African-PREDICT study

“…However, in non-obese normotensive German men (age 25 years), angiotensinogen associated positively with leptin [38], thus suggesting the potential role of RAS in the link between leptin and blood pressure in our study. However, black populations are known to have lower renin, angiotensin I and II levels compared to whites [39,40], possibly explaining the lack of association between DBP and leptin in black men. More research is necessary to establish a link between leptin and the RAS system in Africans.…”

Molecular remodeling of the renin-angiotensin system after kidney transplantation

“… 30 Several other studies have shown that Ang-(1–7) concentrations are often very low or immeasurable in states of health and disease. 31 , 32 While we did not measure ACE2 activity, we are the first to quantify the effector molecules of the alternative RAS in these patients. Our results suggest that Ang-(1–7) might be quickly metabolized to Ang-(1–5) in patients without ACE inhibitors as most patients without RAS blockade or on ARB had detectable Ang-(1–5) levels, indicating an ongoing activity of the alternative RAS axis.…”