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Randomized Controlled Trial
. 2025 Aug 1;43(8):1436-1441.
doi: 10.1097/HJH.0000000000004068. Epub 2025 Jun 5.

Increased formation of angiotensin II from angiotensin I in individuals of African descent

Sanjay K Gandhi  1   2 , Kyung-Soo Kim  2   3 , K Bridget Brosnihan  1 , Nancy J Brown  2   4
Affiliations
Randomized Controlled Trial

Increased formation of angiotensin II from angiotensin I in individuals of African descent

Sanjay K Gandhi et al. J Hypertens. .

Abstract

Objective: Activation of the renin-angiotensin-aldosterone system (RAAS) and African ancestry are both associated with increased end-organ damage in hypertension. An insertion (I)/deletion (D) polymorphism in the gene encoding the angiotensin-converting enzyme (ACE) has been associated with ACE activity. This study tested the hypothesis that ancestry or ACE I/D genotype affects the conversion of angiotensin (Ang) I to Ang II and blood pressure, renal plasma flow, and aldosterone during Ang I or II infusion.

Methods: Ang I and Ang II were infused in graded doses from 1 to 20 ng/kg/min in a randomized, single-blind, crossover study in salt-replete normotensive participants of self-identified African (Black) or European (white) ancestry who were homozygous for the ACE I/I (7 Black, 8 white) or D/D (8 Black, 8 white) genotype.

Results: ACE activity was significantly increased in ACE D/D vs. ACE I/I individuals regardless of ancestry. The conversion of Ang I to Ang II was increased in Black compared to in white participants, independent of genotype. The pressor and aldosterone responses to Ang I and Ang II did not differ by ancestry or ACE I/D genotype. Basal renal plasma flow was increased in individuals of ACE D/D genotype independent of ancestry but the renal vasoconstrictor response to Ang I and Ang II did not differ by ACE genotype.

Conclusions: The conversion of infused Ang I to Ang II is increased in Black compared to in white individuals. Increased Ang II could contribute to attenuated responses to RAAS interfering drugs and end-organ damage in individuals of African ancestry.

Keywords: aldosterone; ancestry; angiotensin; angiotensin-converting enzyme; blood pressure; renal blood flow; renin.

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References

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