Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0020538 (
hypertension
)
170,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
High salt, Ang II (angiotensin II), and reactive oxygen species enhance progression of chronic kidney disease. We tested the hypothesis that a high salt intake generates specific reactive oxygen species to enhance Ang II contractions of afferent arterioles from mice with reduced renal mass (RRM). C57BL/6 mice were subjected to surgical RRM or sham operations and received 6% or 0.4% NaCl salt diet for 3 months. Ang II contractions were measured in perfused afferent arterioles and superoxide (O
2
-
) and hydrogen peroxide (H
2
O
2
) by fluorescence microscopy. RRM enhanced the afferent arteriolar gene expression for p47
phox
and neutrophil oxidase (NOX) 2 and high salt intake in RRM mice enhanced gene expression for angiotensin type 1 receptors,
POLDIP2
and NOX4 and reduced catalase. High salt in mice with RRM enhanced arteriolar O
2
-
and H
2
O
2
generation and maximal contractions to Ang II (10
-6
mol/L) that were dependent on O
2
-
because they were prevented by gene deletion of p47
phox
and on H
2
O
2
because they were prevented by transgenic smooth muscle cell expression of catalase (tg
CAT-SMC
) and
POLDIP2
gene deletion. Three months of tempol normalized arteriolar reactive oxygen species and Ang II contractions. However, arteriolar contractions to lower concentrations of Ang II (10
-8
to 10
-11
mol/L) were paradoxically inhibited by H
2
O
2
and
POLDIP2
. In conclusion, both O
2
-
from p47
phox
/NOX2 and H
2
O
2
from NOX4/
POLDIP2
enhance maximal arteriolar Ang II contractions from RRM mice during high salt, but H
2
O
2
and NOX4/
POLDIP2
reduce the sensitivity to lower concentrations of Ang II by >100-fold. Tempol prevents all of these changes in function.
Hypertension
2018 11
PMID:High Salt Enhances Reactive Oxygen Species and Angiotensin II Contractions of Glomerular Afferent Arterioles From Mice With Reduced Renal Mass. 3035 8
