Influence of type 1 diabetes mellitus on angiotensin-II converting enzymes and neurodegenerative factors in the hypertensive rat

Hypertension and diabetes are recognized as risks for cerebrovascular disease. The present study examined the expression and regulation of angiotensin-converting enzyme (ACE), ACE2, and chymase in the rat frontal brain cortex to assess their roles in neurodegeneration. Frontal cortex brain tissues from control, streptozotocin-induced diabetic, spontaneously hypertensive rats (SHR), and SHR-diabetic (SHR-D) rats were analyzed using immunoblot and biochemical techniques. The expressions of ACE, ACE2, chymase, neurotrophic factors (brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), glutamine synthetase), apoptotic markers (caspase-3, cytochrome c), and oxidative stress markers were evaluated. ACE, ACE2, and chymase were expressed in all groups. Diabetic and hypertensive rats, alongside elevated chymase levels, exhibited significant ACE upregulation and ACE2 downregulation compared to controls. Neuroprotective factors BDNF, TrkB, and glutamine synthetase were markedly reduced in diabetic and hypertensive-diabetic rats, whereas apoptotic markers (caspase-3, cytochrome c) were significantly increased. Oxidative stress, measured by glutathione (GSH) and thiobarbituric acid reactive substances (TBARS), was higher in diabetic and hypertensive groups than in the controls. The combined effects of ACE upregulation, ACE2 downregulation, and increased chymase expression in the hypertensive-diabetic brain cortex may amplify pathological processes. These changes likely enhance oxidative damage and apoptotic pathways, which contribute to neurodegeneration. This study highlights how oxidative stress and the renin-angiotensin system interact critically in cerebrovascular and neurodegenerative disorders linked to diabetes and hypertension.