The markers related to NET (DNA-histone complex) and kallikrein-kinin system (high-molecular-weight kininogen, prekallikrein, bradykinin) and factor XIIa were measured in 253 patients with diabetes.
Even though captopril effectively reversed the diabetes-induced changes in calcium-binding protein 28-k and vitamin D receptor expression in the kidney as well as the expression of RAS components and bradykinin receptor-2 in bone tissue, treatment with captopril increased the osteoclast-covered bone surface, reduced the osteoblast-covered bone surface, down-regulated the expression of type 1 collagen and transcription factor runt-related transcription factor 2 (markers for osteoblastic functions), and up-regulated the expression of carbonic anhydrase II (marker for bone resorption).
When the angiotensin-converting enzyme is inhibited, bradykinin metabolism is dependent on degradation by neutral endopeptidase, dipeptidyl peptidase IV, and aminopeptidase P. When these enzymes are inhibited, as in treatment of diabetes or in transplant recipients, the incidence of angioedema increases significantly.