title: Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats.
abstract: OBJECTIVE
  Hypertension is a major cause of stroke, and diabetes can increase incidence of this disease. We determined the role played by central angiotensin-(1-7) [Ang-(1-7)] pathway in modulating spontaneously hypertension with diabetic hyperglycemia.
  
  
  METHODS
  Western Blot analysis and ELISA were used to determine the protein expression of Ang-(1-7) and its signal pathway Mas-R-nNOS in the cerebral cortex and hippocampus of spontaneously hypertensive rats (SHR) and control animals. In a subset of animals, diabetic hyperglycemia was induced by systemic injection of streptozotocin (STZ). We analyzed a relationship between the levels of central Ang-(1-7) and plasma brain natriuretic peptide (BNP) indicating a risk of ischemic stroke. We further examined the effects of Ang-(1-7) on arterial blood pressure.
  
  
  RESULTS
  Our findings demonstrated for the first time that administration of STZ 1) attenuates the levels of Ang-(1-7) in the cerebral cortex and hippocampus, which are closely linked to plasma BNP; and 2) leads to downregulation of central Ang-(1-7)-Mas-R-nNOS pathways. Notably, STZ has greater effects in SHR. Additionally, inhibition of oxidative stress can largely improve downregulation of Ang-(1-7) in diabetic SHR. Moreover, central stimulation of Ang-(1-7) pathway or a blockade of oxidative stress improves systolic blood pressure in diabetic SHR.
  
  
  CONCLUSIONS
  The Ang-(1-7) signaling pathway is engaged in the adaptive mechanisms associated with diabetic hypertension, suggesting that enhancing Ang-(1-7)-Mas-R-nNOS system is likely to be beneficial in preventing against cardiovascular and cerebrovascular dysfunction and vulnerability related to spontaneously hypertension, particularly to diabetic hypertension.
authors.affiliation: Department of Cardiology, The Fourth Clinical Hospital of Harbin Medical University, Harbin, China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.forename: Zhongqiao
authors.initials: Z
authors.lastname: Ren
authors.forename: Jinxia
authors.initials: J
authors.lastname: Gu
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013113:Spin Labels; D013599:Systole / Q000187:drug effects
chemical_list: D003497:Cyclic N-Oxides; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D013113:Spin Labels; D020097:Natriuretic Peptide, Brain; D000803:Angiotensin I; D015237:Dinoprost; D052248:Nitric Oxide Synthase Type I; C118790:angiotensin I (1-7); C001803:tempol