High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity

• Published in: Clinical science (1979) Vol. 135; no. 20; pp. 2377 - 2391
• Main Authors: Magalhães, Flávio de Castro, Fernandes, Tiago, Bassaneze, Vinícius, Mattos, Katt Coelho, Schettert, Isolmar, Marques, Fabio Luiz Navarro, Krieger, José Eduardo, Nava, Roberto, Barauna, Valério Garrone, Menezes de Oliveira, Edilamar
• Format: Journal Article
• Language: English
• Published: England 29.10.2021
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Captopril - pharmacology; Endurance Training; Female; Hematopoiesis - drug effects; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - enzymology; Oligopeptides - metabolism; Peptidyl-Dipeptidase A - metabolism; Physical Conditioning, Animal; Physical Endurance; Protein Domains; Rats; Rats, Wistar; Time Factors; Exercise training; erythropoiesis; renin-angiotensin system; ACE activity
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20210739

One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; ∼200%, P=0.0008), early erythroid progenitor colonies (∼300%, P<0.0001) and reticulocytes (∼500%, P=0.0007), and reduced erythrocyte lifespan (∼50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg-1.day-1). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.