Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb;234(2):e13732.
doi: 10.1111/apha.13732. Epub 2021 Oct 2.

Angiotensin-converting enzyme inhibitors stimulate cerebral arteriogenesis

Philipp Hillmeister  1   2 , Stephanie Nagorka  3 , Nora Gatzke  1 , Andre Dülsner  3 , Kangbo Li  1   3 , Mengjun Dai  1   3 , Anja Bondke Persson  3 , Martin A Lauxmann  1   4 , Jonnel Jaurigue  1 , Oliver Ritter  4   5 , Peter Bramlage  6 , Eva Buschmann  7 , Ivo Buschmann  1   2
Affiliations

Angiotensin-converting enzyme inhibitors stimulate cerebral arteriogenesis

Philipp Hillmeister et al. Acta Physiol (Oxf). 2022 Feb.

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Acta Physiol (Oxf). 2022 May;235(1):e13805. doi: 10.1111/apha.13805. Epub 2022 Mar 16. Acta Physiol (Oxf). 2022. PMID: 35293130 No abstract available.

Abstract

Aim: Arteriogenesis constitutes the most efficient endogenous rescue mechanism in cases of cerebral ischaemia. The aim of this work was to investigate whether angiotensin-converting enzyme inhibitors (ACEi) stimulates, and angiotensin II receptor type 1 blockers (ARB) inhibits cerebral collateral growth by applying a three-vessel occlusion (3-VO) model in rat.

Methods: Cerebral collateral growth was measured post 3-VO (1) by assessing blood flow using the cerebrovascular reserve capacity (CVRC) technique, and (2) by assessing vessel diameters in the posterior cerebral artery (PCA) via the evaluation of latex angiographies. A stimulatory effect on arteriogenesis was investigated for ACEi administration ± bradykinin receptor 1 (B1R) and 2 (B2R) blockers, and an inhibitory effect was analysed for ARB administration. Results were validated by immunohistochemical analysis and mechanistic data were collected by human umbilical vein endothelial cell (HUVEC) viability or scratch assay and monocyte (THP-1) migration assay.

Results: An inhibitory effect of ARB on arteriogenesis could not be demonstrated. However, collateral growth measurements demonstrated a significantly increased CVRC and PCA diameters in the ACEi group. ACEi stimulates cell viability and migration, which could be partially reduced by additional administration of bradykinin receptor 1 inhibitor (B1Ri). ACEi inhibits the degradation of pro-arteriogenic bradykinin derivatives, but combined ACEi + B1Ri + B1Ri (BRB) treatment did not reverse the stimulatory effect. Yet, co-administration of ACEi + BRB enhances arteriogenesis and cell migration.

Conclusion: We demonstrate a potent stimulatory effect of ACEi on cerebral arteriogenesis in rats, presumable via B1R. However, results imply a pleiotropic and compensatory effect of ACEi on bradykinin receptor-stimulated arteriogenesis.

Keywords: angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; blood flow; bradykinin receptor; brain; cerebral arteriogenesis; collateral growth.

PubMed Disclaimer

Comment in

References

REFERENCES

    1. Group WCRCW. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. Lancet Glob Health. 2019;7(10):e1332-e1345.
    1. Bieber M, Werner RA, Tanai E, et al. Stroke-induced chronic systolic dysfunction driven by sympathetic overactivity. Ann Neurol. 2017;82(5):729-743.
    1. Bang OY, Saver JL, Kim SJ, et al. Collateral flow predicts response to endovascular therapy for acute ischemic stroke. Stroke. 2011;42(3):693-699.
    1. Hillmeister P, Lehmann KE, Bondke A, et al. Induction of cerebral arteriogenesis leads to early-phase expression of protease inhibitors in growing collaterals of the brain. J Cereb Blood Flow Metab. 2008;28(11):1811-1823.
    1. Marks MP, Lansberg MG, Mlynash M, et al. Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke. 2014;45(4):1035-1039.

Publication types

Substances

LinkOut - more resources