Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats.

Abstract

BACKGROUND/AIMS:

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: He Li, Xian Liu, Zhongqiao Ren, Jinxia Gu, Yingjie Lu, Xiaoyun Wang, Lan Zhang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 40 Issue 5 Pg. 1186-1197 ( 2016) ISSN: 1421-9778 [Electronic] Germany
• PMID: 27960152 (Publication Type: Journal Article)
• Copyright: © 2016 The Author(s) Published by S. Karger AG, Basel.

Chemical References

• Cyclic N-Oxides
• Peptide Fragments
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Receptors, G-Protein-Coupled
• Spin Labels
• Natriuretic Peptide, Brain
• Angiotensin I
• Dinoprost
• Nitric Oxide Synthase Type I
• angiotensin I (1-7)
• tempol

Topics

• Angiotensin I (metabolism)
• Animals
• Blood Pressure (drug effects)
• Brain (drug effects, metabolism, pathology)
• Cyclic N-Oxides (pharmacology)
• Diabetes Mellitus, Experimental (blood, complications, metabolism)
• Dinoprost (metabolism)
• Heart Rate (drug effects)
• Hyperglycemia (blood, complications, metabolism)
• Natriuretic Peptide, Brain (blood)
• Nitric Oxide Synthase Type I (metabolism)
• Oxidative Stress (drug effects)
• Peptide Fragments (metabolism)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (metabolism)
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptors, G-Protein-Coupled (metabolism)
• Signal Transduction (drug effects)
• Spin Labels
• Systole (drug effects)