Question: 

Recent studies suggest that angiotensin II (ANG II)-dependent hypertension may critically involve the activation of immune cells. A newly detected mode of action of angiotensin II is the activation of polymorphonuclear neutrophils to secrete myeloperoxidase (MPO). We therefore hypothesized that MPO may be specifically involved in the development of vascular dysfunction in ANG II-dependent hypertension.

Methods: 

Three different groups of male MPO knockout (KO) and C57Bl/6J (control) mice were treated for 14 days with either subcutaneous infusion of ANG II (1.5 ng/min per g of body weight via osmotic minipumps), deoxycorticosterone acetate (50 mg via release pellets) combined with 1% NaCl solution in drinking water (DOCA-salt), or infusion of 0.9% NaCl via osmotic minipumps (SHAM). On day 14, aortic rings were investigated in tissue bath chambers for relaxation responses to acetylcholine (endothelium-dependent) or glyceroltrinitrate (NTG; endothelium-independent).

Results: 

In control mice, both endothelium-dependent and endothelium-independent relaxation was significantly attenuated in ANG II-treated aortic rings compared to SHAM treatment. Less distinctive but also significant effects were seen after DOCA-salt treatment. Endothelium-independent relaxation was significantly less impaired in MPO KO treated with ANG II; a similar, but not significant trend was also observed for endothelium-dependent relaxation. No significant differences between both genotypes were found in DOCA-salt or SHAM treated animals.

Conclusions: 

These findings suggest that MPO plays an important role in ANG II-dependent hypertension by modifying vascular tone via catalytic consumption of NO and non NO-dependent mechanisms. This effect seems to be specifically related to an activation of MPO release from polymorphonuclear neutrophils and/or activation of MPO by ANG II, highlighting a so far underrecognized cytokine-like, leukocyte activating property of Ang II.