Angiotensin-converting enzyme inhibitors stimulate cerebral arteriogenesis

Area of Science:

• Neuroscience
• Cardiovascular Biology
• Pharmacology

Background:

• Arteriogenesis is the primary endogenous mechanism for recovery from cerebral ischemia.
• Understanding factors that promote collateral growth is crucial for developing effective stroke treatments.

Purpose of the Study:

• To investigate the effect of angiotensin-converting enzyme inhibitors (ACEi) on stimulating cerebral arteriogenesis.
• To determine if angiotensin II receptor type 1 blockers (ARB) inhibit cerebral collateral growth.
• To explore the role of bradykinin receptors in ACEi-mediated arteriogenesis.

Main Methods:

• A three-vessel occlusion (3-VO) rat model was used to induce cerebral ischemia.
• Cerebral collateral growth was assessed by measuring cerebrovascular reserve capacity (CVRC) and posterior cerebral artery (PCA) diameters.
• Effects of ACEi and ARB, with or without bradykinin receptor blockers, were evaluated.
• Mechanistic studies included cell viability and migration assays.

Main Results:

• ACEi significantly increased CVRC and PCA diameters, indicating enhanced collateral growth.
• An inhibitory effect of ARB on arteriogenesis was not demonstrated.
• ACEi stimulated endothelial cell viability and monocyte migration, partly mediated by bradykinin receptor 1 (B1R).
• Combined ACEi and bradykinin receptor blockade still enhanced arteriogenesis and cell migration.

Conclusions:

• ACEi exert a potent stimulatory effect on cerebral arteriogenesis in rats, likely through B1R.
• ACEi demonstrate a pleiotropic effect on bradykinin receptor-mediated arteriogenesis.
• These findings highlight ACEi as a potential therapeutic agent for promoting recovery from cerebral ischemia.