Kinin-mediated activation of endothelial no formation: possible role during myocardial ischemia.

Endothelial cells produce a variety of factors involved in the control of vascular tone, platelet activation and cell growth, one of the most important being nitric oxide (NO). Although continuously produced in response to fluid shear stress, the release of NO from these cells can be enhanced further by humoral stimuli, such as bradykinin. This is the result of a chain of complex intracellular events involving changes in Ca2+, pH and protein phosphorylation. Endothelial cells are also capable of synthesizing bradykinin from an endogenous source, the release of which is markedly enhanced under hypoxic conditions. The finding that ACE inhibitors promote the local accumulation of the peptide and increase its efficacy at the receptor level may partly explain the potent anti-ischemic and cardioprotective effects of these drugs.